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Full-Text Articles in Medicine and Health Sciences

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes Dec 2014

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …


Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes Dec 2014

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …


Pancreatic Ribonuclease Functions As An Epidermal Growth Factor Receptor Ligand Independently Of Its Enzyme Activity And Contributes To Cetuximab Resistance, Heng-Huan Lee Aug 2014

Pancreatic Ribonuclease Functions As An Epidermal Growth Factor Receptor Ligand Independently Of Its Enzyme Activity And Contributes To Cetuximab Resistance, Heng-Huan Lee

Dissertations & Theses (Open Access)

Ribonuclease (RNase) with its catalytic enzyme activity to degrade RNAs has been shown as a diagnostic serum marker for pancreatic cancer and has also been suspected to have an unidentified cell surface receptor. Epidermal growth factor receptor (EGFR), a well-characterized receptor tyrosine kinase is an effective therapeutic target in multiple cancer types. However, clinical trials targeting EGFR have not demonstrated improved therapeutic efficacy in pancreatic cancer. Here, we show that both bovine pancreatic RNase A (bRNaseA) and human RNase 5 (hRNase5) act as EGFR ligands and directly activate EGFR to promote epithelial-mesenchymal transition. This ligand-like activity is independent of RNases’ …


Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso May 2014

Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso

Dissertations & Theses (Open Access)

T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR+ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, …


Mechanisms Underlying Distinct Egfr Versus Fgfr-3 And -1 Dependency In Human Bladder Cancer Cells, Tiewei Cheng May 2014

Mechanisms Underlying Distinct Egfr Versus Fgfr-3 And -1 Dependency In Human Bladder Cancer Cells, Tiewei Cheng

Dissertations & Theses (Open Access)

The epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) are activated by gene amplification, mutation and overexpression in bladder cancer, which drives tumor development and progression. Both EGFR and FGFR inhibitors are currently being tested in clinical trials. However, bladder cancer (BC) cells show remarkably heterogeneous sensitivities to both inhibitors, and the molecular determinants of this heterogeneity are presently unclear. Therefore, in this study, using selective EGFR and FGFR inhibitors in BC cells, we demonstrated that FGFR3 and FGFR1 play largely non-overlapping roles in mediating proliferation and invasion in the distinct “epithelial” and “mesenchymal” subsets of human …


Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden Jan 2014

Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden

Wayne State University Dissertations

Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment …


Chmp1 Negatively Regulates Epidermal Growth Factor Signaling In The Drosophila Wing, Meagan Elisabeth Valentine Jan 2014

Chmp1 Negatively Regulates Epidermal Growth Factor Signaling In The Drosophila Wing, Meagan Elisabeth Valentine

Theses, Dissertations and Capstones

A critical step in cellular signaling through transmembrane receptors is the down-regulation of activated receptors through the multivesicular body (MVB) pathway to the lysosome. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Though the ESCRT-III complex provides the core function of the ESCRT machinery, it is the least characterized of the ESCRT complexes. The Chmp1 protein is an ESCRT-III component and a putative tumor suppressor that has been linked to pancreatic and renal cancers in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not …