Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 17 of 17
Full-Text Articles in Medicine and Health Sciences
Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare
Molecular Mechanism And Impact Of Sox2 Regulation By The Transforming Growth Factor-Ss Members In Ovarian Cancer Survival And Metastasis, Zainab Shonibare
All ETDs from UAB
Ovarian cancer is the second most common and deadliest cancer of the female reproductive system affecting women in the United States and worldwide. The poor survival outcome seen in ovarian cancer is attributed to the subtleness of its early-stage symptoms, resulting in a majority of patients at initial diagnosis presenting with an advanced-stage disease with metastasis to other parts of the body. Hence, there is an urgent need to better understand the molecular etiology of metastasis to help develop effective therapeutic options and improve clinical outcomes in ovarian cancer patients. Ovarian cancer, an intra-abdominal cancer, most preferably undergoes metastasis via …
Targeting Oncogenic Microrna In Lung Cancer, Mackenzie Lauren Davenport
Targeting Oncogenic Microrna In Lung Cancer, Mackenzie Lauren Davenport
All ETDs from UAB
Lung cancer is the leading cause of cancer-related death both in the United Statesand the world. While several genetic drivers of lung cancer have been identified, major improvements in patient outcome are lacking, highlighting the need to further understand the genetic and molecular mechanisms of this disease. The microRNA miR-31 has been implicated in oncogenesis in a variety of cancer types, and prior data from our laboratory has shown it to be overexpressed in human lung adenocarcinoma tumors compared to normal lung, high miR-31 levels correlate with decreased patient survival, and overexpression of miR-31 alone in the mouse lung epithelium …
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 …
Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried
Identification Of Two Spop-Mediated Pathways In Prostate Cancer Progression, Joshua Fried
All ETDs from UAB
Prostate cancer is one of the most common malignancies and causes of cancer related death in men. Morbidity is primarily attributed to late-stage and metastatic disease. Re-cent genomic screening studies have revealed that the Speckle type Poz Protein (SPOP) is the most frequently altered gene by missense mutations in prostate cancer. Interestingly, all of the identified mutations were located in the substrate binding domain of SPOP. Here, two pathways highlighting the impact of SPOP mutation on prostate cancer are pre-sented. First, evidence showing that one of the naturally occurring SPOP mutations, ser-ine 119 to asparagine (S119N), induces radiosensitivity and an …
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 …
The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter
The Role Of Adipocytes And Osteocytes In Multiple Myeloma Progression, Timothy Nathan Trotter
All ETDs from UAB
Multiple myeloma (MM) is a hematological malignancy of plasma cells that is intrinsically tied to the bone marrow (BM). Many cells in the BM microenvironment have been studied in MM, yet there is still much progress to be made. Recent work has revealed two new potential cellular targets in MM: adipocytes and osteocytes. Both are endocrine cells and secrete many molecules that regulate other cells proximally and systemically. Our lab previously showed that MM cells shift osteoblast precursor cells towards adipogenesis through soluble molecules alone. Recent findings also revealed that osteocyte apoptosis is enhanced in MM patients compared to healthy …
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 …
Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell
Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell
All ETDs from UAB
It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …
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 …
Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby
Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby
All ETDs from UAB
Curative approaches for metastatic breast cancer remain elusive. Adiponectin is the most abundant of the adipocyte-secreted adipokines, and there is recent interest in development of adiponectin-based therapies for this disease. Yet, while multiple epidemiological studies have indicated that low levels of circulating plasma adiponectin portend poorer prognosis, recent work has reported that elevated adiponectin expression in breast tissue correlates with advanced disease. Further, isoform-specific roles of this molecule are not well understood. Thus, the overarching purpose of this work was to elucidate how adiponectin isoforms contribute to the microenvironmental regulation of the early steps of breast cancer metastasis. We show …
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: …
Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft
Alpha-Camkii-Induced Vegf Expression Is Critical For The Growth Of Human Osteosarcoma, Paul Glenn Daft
All ETDs from UAB
Osteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in OS treatment, more specific molecular targets are needed. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation. Here, we show that α-CaMKII is highly expressed in primary OS tissue, and α-CaMKII deletion in human OS cell lines significantly reduces tumor burden in vivo. This inhibition of α-CaMKII results in decreased vascular endothelial growth factor (VEGF) protein secretion. Highly aggressive OS cells express VEGF receptor …
Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook
Understanding Molecular Mechanisms Of Breast Cancer Metastasis Using Genetically-Engineered Mice, Leah M. Cook
All ETDs from UAB
Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells metastasize to distant organ sites. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. Thus Brms1 transgenic mice (derived on C57BL/6 background) were generated by utilizing MMTV promoter expression (for mammary-selective overexpression) or the beta-actin promoter (for ubiquitous …
Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds
Brms1 Coordinately Regulates Microrna To Suppress Breast, Mick D. Edmonds
All ETDs from UAB
The majority of cancer related mortality is attributed to complications associated with metastatic disease. Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple cancer types in vivo and loss of nuclear BRMS1 is associated with ER-negative cancers and a high rate of proliferation. Many groups have shown BRMS1 to regulate the expression of multiple metastatic genes, yet until now no one has been able to account for how these many changes in gene expression occur. In this work, we report that BRMS1 regulates a select set of genes called microRNA (miRNA), and these miRNA themselves can regulate metastasis. Using …
The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon
The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon
All ETDs from UAB
Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …
Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine
Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine
All ETDs from UAB
Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …
Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya
Role Of Syndecan-1 As Key Regulator Of Multiple Myeloma Pathogenesis, Yekaterina Borisovna Khotskaya
All ETDs from UAB
Syndecan-1 (CD138), a transmembrane heparan sulfate-bearing proteoglycan, is expressed at high levels on most myeloma cells and is shed into the microenvironment. In patients, high levels of serum syndecan-1 are indicative of poor prognosis and elevation of shed syndecan-1 in animal models dramatically enhances tumor growth, angiogenesis and metastasis. Because syndecan-1 is a key regulator of myeloma pathogenesis, we hypothesized that reduction of syndecan-1 levels expressed by the myeloma cells will block their growth and dissemination. Syndecan-1 knockout and knockdown variants of two human myeloma cell lines, CAG and RPMI-8226, were developed using short hairpin RNA (shRNA) technology. In vitro, …