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Full-Text Articles in Medicine and Health Sciences
Understanding Financial Hardship In Women With Breast Cancer, Courtney Williams
Understanding Financial Hardship In Women With Breast Cancer, Courtney Williams
All ETDs from UAB
Individuals with cancer are at risk of material, psychological, and behavioral financial hardship due to costly new treatments, increasing time on treatment, and longer survival. Breast cancer is an ideal environment to study financial hardship. Treatment options for metastatic breast cancer are heterogeneous due to differences in patient characteristics, disease biology, and because it has the largest number of treatment options of any metastatic cancer. In early stage breast cancer, treatment options include multimodality treatments, including surgery, radiation, and medical therapy (chemotherapy, hormone therapy, targeted therapy), with the choice for each modality being dependent on the other modality decisions. Despite …
Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson
Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson
All ETDs from UAB
In the US, nearly 40% of adults have obesity. Further, obesity is known toincrease the risk for development, recurrence, and mortality associated with multiple types of cancer. However, despite such high prevalence, the impact of excess body weight on anti-tumor immunity and response to immunotherapeutics remains poorly and incompletely understood. In order to address these deficiencies, we have utilized multiple approaches to study obesity-associated perturbations in the immunogenetic, soluble protein, and cellular profiles of mice bearing mammary tumors and treatment naive human subjects with clear cell renal cell carcinoma (ccRCC). In a pre-clinical murine model of breast cancer, we find …
Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa
Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa
All ETDs from UAB
Hypoxia within solid tumors presents as a barrier to the effectiveness of cancer treatment. Hypoxia has been implicated in cancer cell resistance to standard therapies used in the clinic to treat breast cancer. Additionally, the treatment resistance mechanisms in cancer cells are exacerbated by oncogenic pathways that enable adaptation to the hypoxia and facilitate therapy resistance. Cancer cells often co-opt signaling pathways essential for embryonic development as a defense against cellular attacks. Hedgehog (Hh) signaling pathway is one of such embryonic development pathways that have been implicated in mitigating cancer growth, metastasis, and resistance to therapy. Hh signaling pathway promotes …
Exploring The Link Between Dietary Fiber, The Gut Microbiota And Estrogen Metabolism Among Women With Breast Cancer, Ayse G. Zengul
Exploring The Link Between Dietary Fiber, The Gut Microbiota And Estrogen Metabolism Among Women With Breast Cancer, Ayse G. Zengul
All ETDs from UAB
Breast cancer continues to be a very prevalent disease and impacts over 260,000 new patients per year in the United States. The gut microbiota composition may affect breast cancer risk by modulating various hormonal metabolites including endogenous estrogens. Dietary factors impact gut microbial ecology and influence the regulation of estrogen metabolism. Current evidence supports the potential role of dietary fiber in breast cancer prevention and its possible modulating influence on serum estrogen levels through the gut microbiota associated with β-glucuronidase activity. However, this mechanism is not clearly understood. In this study, we aimed to explore the associations between dietary fiber, …
Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden
Mitochondria-To-Nucleus Retrograde Signaling And Its Role In Cancer, Trevor Carden
All ETDs from UAB
Mitochondrial dysfunction is considered a hallmark of cancer. Mitochondria are essential, cellular organelles that participate in processes including energy production, calcium homeostasis and steroid metabolism. Mitochondria have been more recently appreciated for their role in cellular signaling, bringing about a greater understanding of their role in many diseases including cancer. Retrograde signaling is a mechanism by which the nucleus responds to mitochondrial dysfunction by modulating its own transcriptional programs to maintain metabolic and cellular processes. Many genes have already been identified as participants in or mediators of this signaling mechanism; these include cell signaling, metabolic and structural genes as well …
Elucidating The Role Of Hedgehog Signaling In Modulating Macrophage Function In Breast Cancer, Ann Hanna
Elucidating The Role Of Hedgehog Signaling In Modulating Macrophage Function In Breast Cancer, Ann Hanna
All ETDs from UAB
In the tumor microenvironment, breast cancer cells participate in crosstalk with the surrounding stroma. This tumoral-stromal interaction forms a balance that dictates tumor suppressing or tumor promoting response mechanisms. Macrophages in the tumor microenvironment are plastic and can mediate several functions depending on their activation states. Tumor associated macrophages co-exist as two major phenotypes: anti-tumorigenic and immune-eliciting classically activated M1 as well as tumor-promoting and immune-suppressive alternatively activated M2 macrophages. Alternatively activated macrophages are specifically associated with more aggressive stages and poor clinical outcomes in breast cancer patients as they suppress the tumoricidal properties of the immune system, thus facilitating …
Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo
Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo
All ETDs from UAB
Background: There are nearly 3.5 million breast cancer survivors in the U.S., and approximately 10% are diagnosed prior to age 45 and considered “young.” The overall five-year survival rate for breast cancer survivors is approaching 90%. Living longer, many breast cancer survivors are at risk for developing cardiovascular disease due to cancer treatment, such as anthracyclines and/or trastuzumab. This study’s purpose was to examine cardiovascular disease risk, measured using excess heart age, among young breast cancer survivors. Methods: A retrospective, two-year longitudinal design was used to review electronic medical records of breast cancer survivors diagnosed between 30 and 44 years …
Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt
Elucidating The Physiologic And Prognostic Significance Of N-Myc And Stat Interactor Using Models Of Mammary Development And Metastasis, Hawley Christine Pruitt
All ETDs from UAB
Distant metastasis of breast carcinoma reduces the five year survival rate of patients from 90% to a dismal 25%. Although the metastatic cascade has been extensively studied for decades, players that influence the progression of metastatic disease remain elusive. N-MYC and STAT Interactor (NMI) is a gene previously demonstrated by Devine et. al. to be downregulated with metastatic progression of breast cancer. However, due to the lack of a relevant genetic model, details of biological consequence of the loss of expression of this gene were unknown. We have constructed and characterized a mammary specific Nmi knock out mouse to elucidate …
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
Regulation Of Breast Cancer Metastasis By Sin3 Chromatin Remodeling Complexes, Monica Jeanene Lewis
All ETDs from UAB
Metastasis continues to be the most difficult clinical challenge for breast cancer. Survival rates for patients with metastatic breast cancer have not significantly changed in the past 20 years. Therefore, we need a better understanding of the molecular mechanisms that regulate breast cancer metastasis to develop effective therapies. SIN3 chromatin remodeling complexes have been implicated in breast cancer progression. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions during development. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. To better understand how …
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
Interplay Between Her2, Parp1, And Nf-Κb In Breast Cancer: Potential Therapeutic Implications, Monicka Ewa Wielgos
All ETDs from UAB
We previously reported that HER2+ breast cancers are susceptible to Poly (ADP-Ribose) polymerase inhibitors (PARPi) alone, agents that are efficacious against homologous recombination (HR) deficient tumors. However, this phenomenon was determined to be independent of a HR repair deficiency but rather due to suppression of NF-κB activity and signaling by PARP inhibition. Further, HER2 overexpression itself was necessary and sufficient to confer this susceptibility. Interestingly, PARP1 and phosphorylated RelA/p65 (NF-κB) levels were found to be elevated in human HER2+ breast cancers compared to luminal breast cancers. These data suggest a possible interplay between HER2, PARP1, and NF-κB, and how this …
Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley
Exploiting Novel Interactions With Parp1 In Dna Repair Proficient Human Breast Cancers, Jennifer Anne Stanley
All ETDs from UAB
Breast cancer remains the most frequently diagnosed cancer amongst women worldwide. Despite advances in treatment, patients with more aggressive basal-like and HER2-positive cancer experience high rates of recurrence and necessitate novel therapeutic approaches. A class of inhibitors targeted against poly (ADP-ribose) polymerases (PARP), important DNA repair proteins, are effective in cancers with a defective DNA repair response. As such, extensive preclinical and clinical research has examined their efficacy in these cancers. Although this data is promising, it is only applicable to a lim-ited patient population. The main goal of this dissertation is to expand the utility of these well-tolerated drugs …
Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley
Mitochondrial Genetics And Cellular Metabolism Regulate Tumorigenicity And Metastatic Potential, Kyle Paul Feeley
All ETDs from UAB
Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors combine to influence an individual's predilection for breast cancer and related metastatic tumor formation. The genetic component, in particular, has become the focus of many emergent studies. A renewed focus on cancer metabolism and the Warburg effect has similarly cast a spotlight on the role, if any, of the mitochondrion in directing disease progression. Analysis of the direct contribution of mitochondrial DNA on tumorigenicity is made possible through the use of mitochondrial-nuclear exchange (MNX) mice in which nuclei from normal FVB mice (the background strain of the tg: …
Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley
Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley
All ETDs from UAB
Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …
The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley
The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley
All ETDs from UAB
Transforming growth factor-beta (TGF-beta) negatively regulates mammary gland development and requires Wnt5a to exert some of these effects on mammary gland development. Wnt5a is a non-canonical signaling Wnt that is expressed in all stages of mammary gland development except lactation. Using slow release pellets containing Wnt5a, as well as Wnt5a null tissue, we previously showed that Wnt5a also acts to limit mammary development. Initial studies revealed a potential role for TGF-beta and Wnt5a in regulating mammary gland progenitor cells, indicating they may act to regulate the stem and progenitor cell population. In order to study the role of Wnt5a on …
Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm
Mechanisms By Which Tra-8 Anti-Dr5 Antibody And Chemotherapy Enhance Cytotoxicity In Breast Cancer, Hope M. Amm
All ETDs from UAB
Breast cancer is the second leading cause of cancer-related death in American women and metastatic breast cancer has a 5-year survival rate of only 26%. Current targeted treatments for this disease include anti-estrogen strategies for estrogen receptor positive tumors (~60%) and anti-Her2/Neu strategies for tumors overexpressing this receptor (20-25%). A percentage of breast cancer patients, however, are resistant to these therapies and are left without any effective treatment options. One of the agents currently being investigated to improve breast cancer survival is TRA-8, an agonistic monoclonal antibody to death receptor 5 (DR5), which induces apoptosis in various types of cancer …
Genome Copy Number Profiles Of African-American And European-American Early-Onset Breast Cancer, Tyesha Latrece Farmer
Genome Copy Number Profiles Of African-American And European-American Early-Onset Breast Cancer, Tyesha Latrece Farmer
All ETDs from UAB
Breast cancer is the second leading cause of cancer related death among women in the United States, surpassed only by lung cancer. It is estimated that over 200,000 women developed breast cancer and more than 40,000 died of the disease in 2008 alone. Although the overall incidence of breast cancer is lower in African-American women, the incidence of early-onset breast cancer is higher than that observed in European-American women. African-American women also have higher mortality rates due to this disease than those observed in their European-American counterparts. Breast cancer exhibits heterogeneity at the molecular, cellular, and clinical levels, and the …