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Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons™
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- Blood-Brain Barrier (2)
- Radiation (2)
- Vasculature (2)
- Acute Leukemia (1)
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- Brain Tumor (1)
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- COPII; CRISPR activation (1)
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- Chemoresistance; inflammation; LUBAC; NF-kB; OTULIN; TNF-alpha (1)
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- Ph.D. (1)
- Ph.D. Clinton F. Stewart (1)
- Ph.D. Dianna A. Johnson (1)
- Ph.D. Suzanne J. Baker (1)
- Procollagen (1)
- Protein Kinase C (1)
Articles 1 - 10 of 10
Full-Text Articles in Analytical, Diagnostic and Therapeutic Techniques and Equipment
Tcf4 Is A Key Mediator Of Cell Identity And Oncogenesis In Neuroblastoma, Nour Aljouda
Tcf4 Is A Key Mediator Of Cell Identity And Oncogenesis In Neuroblastoma, Nour Aljouda
Theses and Dissertations (ETD)
Neuroblastomas (NB) are embryonal childhood tumors that derive from the multipotent neural crest cells (NCCs) of the peripheral nervous system. NB accounts for more than 15% of all childhood cancer-related deaths. Despite the most intensive multimodal therapy, more than 50% of patients with high-risk NB relapse with often fatal, resistant disease. Novel therapies are desperately needed to improve cure rates. Previous studies proposed that the deregulation of normal neural crest developmental programs contributes to NB oncogenesis by retaining the highly migratory and proliferative traits of NCCs. Thus, activation or repression of neural crest developmental pathways have been implicated in NB …
Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse, Anthony Brown
Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse, Anthony Brown
Theses and Dissertations (ETD)
Hepatoblastoma is the most common primary liver cancer in infants and young children. Despite being a very rare cancer that accounts for only 0.5-2% if all childhood cancer cases, HB has the largest increase in incidence among childhood cancers in the United States and worldwide. The five-year survival rate of children with the aggressive forms of HB, including those that have developed metastatic or recurrent diseases, is less than 40% due to the lack of effective treatment. We aim to identify targetable mechanisms underlying the progression and drug resistance of high-risk HB. Our recent work on HB mouse and organoid …
Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li
Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li
Theses and Dissertations (ETD)
Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its …
Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib
Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib
Theses and Dissertations (ETD)
Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …
The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle
The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle
Theses and Dissertations (ETD)
CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …
Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia
Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia
Theses and Dissertations (ETD)
Acute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. …
Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood
Theses and Dissertations (ETD)
Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …
The Use Of Preclinical Models To Improve The Treatment Of Retinoblastoma, Katie Marie Nemeth
The Use Of Preclinical Models To Improve The Treatment Of Retinoblastoma, Katie Marie Nemeth
Theses and Dissertations (ETD)
Rodent models play an essential role in the development of new chemotherapeutics and dosing regimes. It is often difficult to carryout a clinical study for pediatric cancers due to the small patient population. Retinoblastoma, a pediatric cancer of the eye, is one example of a pediatric cancer that can benefit from preclinical studies. Over the years various retinoblastoma rodent models have been developed used to test various combination of broad-spectrum systemic chemotherapy. It was found form these studies that the combination of topotecan and carboplatin was effective. However both drugs cause myelosuppression and therefore administrating both of these drugs systemically …
The Role Of Inflammation In The Early Radiation Response, Christy Marie Wilson
The Role Of Inflammation In The Early Radiation Response, Christy Marie Wilson
Theses and Dissertations (ETD)
Radiation is one of the principal treatments for adults and children with brain tumors, and is one of the oldest established treatments for tumors of all types. Currently, the limiting factor for the use of radiation is the effect on normal tissue adjacent to the tumor. Toxicity, including early and late effects from radiation, limits the dose administered to the tumor and reduces the probability of cure. This work has three aims in its attempt to understand and limit early radiation damage: characterize the role of the inflammatory molecules tumor necrosis factor alpha (TNF) and intracellular adhesion molecule-1 (ICAM-1) in …
The Combined Effect Of In-Situ Tumor And Irradiation On Peritumoral Brain Vasculature, Janice Ann Zawaski
The Combined Effect Of In-Situ Tumor And Irradiation On Peritumoral Brain Vasculature, Janice Ann Zawaski
Theses and Dissertations (ETD)
In the USA, 200,000 brain tumors are diagnosed each year with glioma representing 8.4% of the 200,000. The standard treatment for glioma consists of surgical resection, when possible, followed by radiation therapy (RT) and/or chemotherapy. Radiation therapy is one of the most effective treatments of brain tumors; however, the therapeutic ratio of RT is limited by damage to the normal tissue. We hypothesize that tumor growth has an adverse effect on the peritumoral tissue through the angiogenic/inflammatory environment it creates rendering it susceptible to further damage by RT which may be prevented by using anti-angiogenic/anti-inflammatory agents. We have developed a …