Cell and Developmental Biology Commons^™

Cancer Stem Cells In Recurrent And Drug-Resistant Lung Cancers, Raagini Suresh, Shadan Ali, Aamir Ahmad, Philip Philip, Fazlul Sarkar

Honors College Theses

With a 5-year survival rate of less than 20%, lung cancer is a leading cause of cancer-related deaths worldwide. Considering the treatments currently in place, this statistic is frankly shocking. A possible explanation for the disconnect between sophisticated treatments and the survival rate can be found in the Cancer Stem Cell (CSC) hypothesis. The CSC hypothesis suggests the idea of a subpopulation of tumor cells with the abilities of self-renewal, cancer initiation, and further maintenance of tumors. Lung CSCs have been associated with resistance to radiation and chemotherapeutic treatments. CSCs have also been implicated in recurrent cancers; …

Adipocyte-Induced Inflammation In Prostate Tumor Progression In Bone: Role Of Cxcr2 And Osteopontin, Aimalie Lynnette Hardaway

Wayne State University Dissertations

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. Evidence suggests that age and obesity, conditions associated with adipocyte accumulation in the bone marrow, are linked to increased risk of developing PCa and progressing to metastatic disease. Studies presented in this dissertation were based on the hypothesis that metastatic progression in bone is a result of a cooperative effort between bone marrow adipocytes, macrophages, osteoclasts, and PCa cells. We specifically focused on two adipocyte-supplied chemokines, CXCL1 and CXCL2, and bone marrow macrophage-secreted osteopontin as key drivers of pro-inflammatory environment in the bone marrow and important …

Unraveling The Genetic Mechanisms Involved In The Evolution And Development Of The Thoracic Appendages In Insects, Victor Medved

Wayne State University Dissertations

Insects display the greatest amount of structural and functional variation among animal groups, particularly in regard to their appendage morphology. These differences can range from the diverse pigmentation patterns between fore- and hindwings to changes in the size and shape of legs. The greatly enlarged jumping hind leg in crickets and grasshoppers is one of the best known illustrations of such diversity, representing a unique feature for the entire order of these insects (Orthoptera). Previous work from our lab has shown that the homeotic gene Ultrabithorax (Ubx) plays a key role in the enlargement of hind legs not only in …

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome inhibitor-induced …

Developmental Evolution Of The Visual System In The Cave-Adapted Small Carrion Beetle Ptomaphagus Hirtus, Jasmina Kulacic

Wayne State University Theses

Extensive research has been done to date on Drosophila and Tribolium eye development; however, not much is known about the molecular basis of development of extremely reduced and modified eyes in cave insects. Ptomaphagus hirtus represents an emerging model system for studying the changes at the molecular level that occurred during the evolutionary adaptation of the eye to the cave environment. Therefore, I have started exploring the morphology and organization of the reduced P. hirtus eyelet, using immunohistochemistry, laser scanning microscopy, and ultrastructural imaging approaches. My findings demonstrate that the adult eyelet lacks ommatidial subdivision and has a thick, clear …

Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation, Aaron Alexander Burr

Wayne State University Dissertations

Protein Quality Control (PQC) comprises cellular pathways that regulate the turnover of short-lived, misfolded proteins. A main component of PQC is Endoplasmic Reticulum (ER)-Associated Degradation (ERAD), which controls the degradation of proteins synthesized in the ER. Aberrations in ERAD have been linked to malignancies such as sarcomas, breast, and pancreatic carcinomas, as well as neurodegenerative disease. The machinery in this system is complex and while significant progress has been made to understand ERAD, it is not clear how the different components come together, or how they are regulated. HRD1 is a resident ubiquitin ligase that has been proposed as a …

Soy Isoflavones Mediate Radioprotection Of Normal Lung Tissue By Modulating The Radiation-Induced Inflammatory Response, Lisa Marie Abernathy

Wayne State University Dissertations

Radiation-induced lung injury (RILI) is caused by an early inflammatory process triggered by damage to lung parenchyma, epithelial cells, vascular endothelial cells and stroma. Initially, oxidative injuries after radiation induce altered expression of pro-inflammatory cytokines. Infiltrating inflammatory cells are stimulated and activated, producing additional mediators, resulting in a cytokine cascade. The expansion and perpetual activation of inflammatory cells, as well as lung parenchyma, lead to clinical pneumonitis. Activated cells produce molecular mediators and growth factors that affect the proliferation and gene expression of lung fibroblasts. This process leads to increased collagen synthesis and deposition, eventually leading to the development of …