Medicine and Health Sciences Commons^™

Case Of Metastatic Eshophageal Adenocarcinoma Presenting As Multiple Cavitary Lung Lesions, Michael L. Ahrens, Mala Goyal, Shivangi A. Gohil, Shruti Verma, Pratima K. Singh

Continental, MidAmerica, & Mountain Divisions GME Research Day 2024

No abstract provided.

Educational Case: An Invasive Salivary Gland Tumor: Adenoid Cystic Carcinoma Of The Parotid Gland, Jaime Eberle-Singh, Madalina Tuluc, Joanna Sue Yee Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

In Vitro Characterization Of A Novel Murine Model Of Cancerous Progression, Steven D. Scahill, Kelly Jean Sherman, Jessie J. Guidry, Whitney Walkowski, Theresa Nguyen, Durwood B. Ray, David H. Jones, Harry J. Gould, Dennis Paul

School of Graduate Studies Faculty Publications

To evaluate a potentially valuable tool to study cancer progression and metastasis, we characterized a novel murine model composed of a parental oncogene-transformed embryonic fibroblast line and five cell lines isolated from progressively advanced tumors. Lines derived from distant metastases displayed significantly greater rates of motility, invasiveness, and extracellular acidification than lines derived from a primary tumor or local metastases. A comprehensive proteomic analysis of these cells showed numerous oncogenes to be upregulated and tumor suppressors to be downregulated in the advanced lines, and provided novel targets for future examination. The first cell line capable of extravasation displayed particularly high …

Induction Of Hypopituitarism Following Ipilimumab/ Nivolumab Therapy Followed By Radiation In The Treatment Of Metastatic Scalp Melanoma, Joshua K. Salabei, Dhaval Upadhyay, Sripal A. Padam

HCA Healthcare Journal of Medicine

Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to …

Veru-111 As An Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer And Evaluation Of Novel Tubulin Inhibitors For Cancer Therapy, Shanshan Deng

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …

The Role Of Kidney Injury Molecule-1 In The Metastasis Of Renal Cell Carcinoma, Jasper Lee

Electronic Thesis and Dissertation Repository

Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by >90% of RCC tumours. Preliminary data mined from The Cancer Genome Atlas RNA-sequencing database indicates that KIM-1 overexpression predicts overall survival in patients. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to the lungs. In vitro invasion and in vivo metastasis assays were performed to investigate the metastatic potential of KIM-1-expressing cells, and RNA-seq was conducted to identify differentially expressed genes between …

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

Dissertations & Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …

Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock

Theses and Dissertations (ETD)

Hypoxia is a hallmark of most solid tumors. In response to hypoxic stress tumor cells adapt by regulating survival, metabolism and angiogenesis. The heterodimeric HypoxiaInducible Factor (HIF) transcription factors are the master regulators of this response. HIFs play key roles in many critical aspects of cancer biology including angiogenesis, stem cell maintenance, metabolic reprogramming, invasion, metastasis and resistance to radiation therapy and chemotherapy. Overexpression of HIF-1α and HIF-2α has been documented in multiple human cancers and HIF-1 protein is over-expressed in ~30% of primary breast tumors and ~70% of metastases, which independently correlates with poor prognosis and decreased survival in …

Imaging Breast Cancer Progression And Lymph Node Metastases In Murine Models Using Mri And Magnetic Nanoparticles, Vasiliki Economopoulos

Electronic Thesis and Dissertation Repository

Most breast cancer related deaths are caused by the spread or metastasis of the primary tumor to distant sites in the body. The lymph nodes are one of the first places where metastases can be detected and are frequently examined for macroscopic metastases to help determine course of treatment for patients. However, little is known about the significance of microscopic metastases and disseminated individual cancer cells within the nodes. The goal of this work was to use MRI to monitor the development of primary tumors and lymphatic metastases in models of breast cancer.

In this thesis, we examined the MRI …

Inhibition Of Breast Cancer Angiogenesis And Metastasis Ay Targeting Hypoxia-Inducible Factor-1Α, Chikezie O. Madu

Theses and Dissertations (ETD)

The current clinical chemotherapy agents are not ideal for breast cancer as they are not curative, but only provide a modest extension of survival with sometimes a severely adverse effect on the patient’s quality of life. There is, therefore, an urgent need to search for new and more effective anti-breast cancer drugs. However, the existing screening system is inefficient and time-consuming despite the extremely large amount of small molecule compounds in database currently available, and thereby hindering the effort for selecting new and effective anti-cancer drugs.

The majority of locally advanced solid tumors contain regions of reduced oxygen availability. Hypoxia …

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …