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Articles 1 - 15 of 15
Full-Text Articles in Life Sciences
A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard
A Representative Clinical Course Of Progression, With Molecular Insights, Of Hormone Receptor-Positive, Her2-Negative Bone Metastatic Breast Cancer, Elizabeth Magno, Karen M. Bussard
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Despite treatment advances, breast cancer remains a leading cause of death of women in the United States, mostly due to metastatic disease. Bone is a preferential site for breast cancer metastasis, and most metastatic breast cancer patients experience bone involvement at the time of death. The majority of patients with bone metastatic breast cancer are first diagnosed with and treated for early-stage disease, and from development of early-stage breast cancer to the recurrence of cancer in the bones, up to 30 years may elapse. Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. …
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo
Legacy Theses & Dissertations (2009 - 2024)
The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …
Primary Lung Carcinoid Metastatic To The Breast, Marianna Zagurovskaya, Karen Tran-Harding, Richard Gibbs
Primary Lung Carcinoid Metastatic To The Breast, Marianna Zagurovskaya, Karen Tran-Harding, Richard Gibbs
Radiology Faculty Publications
Lung carcinoid tumors account for approximately 2% of lung cancers, with 10% of the tumors represented by the atypical type. While atypical carcinoids are metastatic to intrathoracic lymph nodes in approximately half of the cases on the initial presentation, distant metastases are seen in only 20% of the patients and are found most frequently in bones, liver, adrenal glands, and brain. We present a case of an unusual metastatic disease to the breast in 51-year-old female who developed a new breast mass 2 years after left lower lobectomy due to atypical carcinoid tumor. Atypical pulmonary carcinoid metastases to the breast …
Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal
Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal
Legacy Theses & Dissertations (2009 - 2024)
The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …
The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky
The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky
Legacy Theses & Dissertations (2009 - 2024)
Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …
Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews
Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews
Legacy Theses & Dissertations (2009 - 2024)
A strong correlation between vitamin D deficiency and increased breast cancer incidence and mortality has been well established, leading researchers to further examine the possibility of using vitamin D in treatment and prevention strategies. Our long term goal is to elucidate the mechanisms by which vitamin D pathway signaling impacts on breast cancer. Generation of the high-affinity vitamin D receptor (VDR) ligand 1,25-dihydroxyvitamin D (1,25-D) from 25-hydroxyvitamin D (25-D) is mediated by CYP27B1 which is present and developmentally regulated in multiple tissues including the mammary gland. We utilized transgenic mouse models combined with diet-induced vitamin D deficiency to determine whether …
The Lipogenic Phenotype Of Her2/Neu-Positive Breast Cancer Cells, Jan Martin Baumann
The Lipogenic Phenotype Of Her2/Neu-Positive Breast Cancer Cells, Jan Martin Baumann
Legacy Theses & Dissertations (2009 - 2024)
Recent work has shown that HER2/neu-positive breast cancer cells rely on a unique Warburg-like metabolism for survival and aggressive behavior. These cells are dependent on fatty acid (FA) synthesis, show markedly increased levels of stored fats and disruption of the synthetic process results in apoptosis. Supplementation of the growth media with physiological concentrations of saturated FAs induces cell death, whereas HER2-normal cells are not affected. This is particularly interesting in the context of new epidemiological data showing that a diet rich in saturated FAs is positively correlated with the development of HER2-negative disease, but not HER2/neu-positive disease.
Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta
Molecular Actions Of The Vitamin D Receptor In Breast Cancer, Erika Laporta
Legacy Theses & Dissertations (2009 - 2024)
1,25-Dihydroxyvitamin D (1,25D) exerts anti-cancer actions through the vitamin D receptor (VDR) but the specific targets that mediate these effects remain to be defined. In these studies, growth and genomic responses to 1,25D were evaluated in a cellular model system derived from mammary tumors generated in VDR knockout (KO) and wildtype (WT) mice. WT145 cells (derived from WT tumors) expressed VDR and were growth inhibited by 1,25D, whereas KO240 cells (derived from VDRKO tumors) lacked VDR and were not growth inhibited by 1,25D. KO240 cell clones stably expressing VDR (KOhVDR cells) were sensitized to 1,25D mediated growth arrest. Genomic profiling …
The P38 Alpha Stress-Activated Protein Kinase Pathway In Mammary Gland Development And Cancer, Huei-Chi Wen
The P38 Alpha Stress-Activated Protein Kinase Pathway In Mammary Gland Development And Cancer, Huei-Chi Wen
Legacy Theses & Dissertations (2009 - 2024)
Breast tumors arise from preinvasive lesions consisting of abnormal epithelial cells that accumulate within the mammary duct. However, the initiating steps and underlying pathways leading to the formation of these early stages of breast carcinoma, such as ductal carcinoma in situ (DCIS), is not fully understood.
Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert
Legacy Theses & Dissertations (2009 - 2024)
The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).
A Breast Cancer Stem Cell Model Created From Mmtv-Pymt Mice Applicable To Human Breast Cancer, Denise Grant Lanza
A Breast Cancer Stem Cell Model Created From Mmtv-Pymt Mice Applicable To Human Breast Cancer, Denise Grant Lanza
Legacy Theses & Dissertations (2009 - 2024)
Cancer stem cells are the seeds of tumor growth, but there are limited cell-based methods that exist to study the properties of these cells. To create a model of breast cancer stem cells, we isolated tumors from MMTV-PyMT mice. Two out of the four different cell types isolated survived in culture, CD44+CD24- and CD24+CD49f+CD44low. We found that we could initiate tumors with as few as 10 cells injected subcutaneously in the hind leg or orthotopically in the cleared fat pad with CD24+ cells. However, we could not initiate tumors with injection of CD24- cells. We found a requirement for TICs …
Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren
Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren
Arthur M. Mercurio
Defects in the expression or function of the calcium dependent cell-cell adhesion molecule E-cadherin are common in invasive, metastatic carcinomas. In the present study the response of aggregates of breast epithelial cells and breast and colon carcinoma cells to forces imposed by laminar flow in a parallel plate flow channel was examined. Although E-cadherin negative tumor cells formed cell aggregates in the presence of calcium, these were significantly more likely than E-cadherin positive cell aggregates to disaggregate in response to low shear forces, such as those found in a lymphatic vessel or venule (< 3.5 dyn/cm2). E-cadherin positive normal breast epithelial cells and E-cadherin positive breast tumor cell aggregates could not be disaggregated when exposed to shear forces in excess of those found in arteries (> 100 dyn/cm2). E-cadherin negative cancer cells …
Glycogen Synthase Kinase-3 Is An Endogenous Inhibitor Of Snail Transcription: Implications For The Epithelial-Mesenchymal Transition, Robin E. Bachelder, Sang-Oh Yoon, Clara Franci, Antonio Garcia De Herreros, Arthur M. Mercurio
Glycogen Synthase Kinase-3 Is An Endogenous Inhibitor Of Snail Transcription: Implications For The Epithelial-Mesenchymal Transition, Robin E. Bachelder, Sang-Oh Yoon, Clara Franci, Antonio Garcia De Herreros, Arthur M. Mercurio
Arthur M. Mercurio
We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial-mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFkappaB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. …
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 …
An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert
An Rnai Screen Targeting The Protein Tyrosine Kinases Identifies Bruton's Tyrosine Kinase (Btk) As A Breast Cancer Cell Survival Factor, Cheryl Lynne Eifert
Legacy Theses & Dissertations (2009 - 2024)
The receptor protein tyrosine kinases (RPTKs) and the non- receptor protein tyrosine kinases (PTKs) are among the most commonly up-regulated genes found in all types of cancers. Although, a large body of data implicates a majority of tyrosine kinases (TKs) in cancer, few have been extensively evaluated for any potential therapeutic benefit in any of the many subtypes of breast cancer. We have used RNA interference (RNAi) to perform a large-scale loss-of-function analysis to facilitate the identification of individual factors necessary for the survival of an ErbB2 positive breast cancer cell line. We have found that 30% of the TKs …