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Articles 1 - 30 of 32
Full-Text Articles in Medicine and Health Sciences
Lymphatic Dysfunction And Associated Systemic Inflammation In Lymphedema, Assessed By Nirf-Li Imaging And Plasma Cytokine/Chemokine Analysis, Anna Vang
Dissertations & Theses (Open Access)
Breast cancer-related lymphedema (BCRL) manifests as swelling of the upper extremities and trunk as a result of lymphatic fluid buildup due to radiation therapy (RT), surgical lymph node removal, or chemotherapy. As there is currently no cure, BCRL treatment aims to improve quality of life (QOL). First-line treatment involves specialized massage therapy and the use of compression garments. Second-line treatments include reparative lymphatic microsurgeries such as lymphovenous bypass (LVB) and/or vascularized lymph node transplant (VLNT). There is a need for better understanding of the etiology of BCRL and lymphatic microsurgery outcomes. Blood specimens and near-infrared fluorescent lymphatic imaging (NIRF- LI)data …
Development Of Quantitative Molecular Photoacoustic Imaging For Noninvasive Cancer Diagnostics, Cayla Zandbergen
Development Of Quantitative Molecular Photoacoustic Imaging For Noninvasive Cancer Diagnostics, Cayla Zandbergen
Dissertations & Theses (Open Access)
Traditional diagnostic imaging provides clinicians with anatomical information that guides both diagnosis and treatment planning; however, once a tumor has progressed enough to be visible, it has often reached an advanced stage. Molecular imaging techniques allow for real-time visualization of chemical and biological processes via imaging of specific biomarkers, which can facilitate detection of malignancies before they become visible. One biomarker of interest is blood oxygen saturation (SO2) due to its correlation with hypoxia, which is associated with increased tumor malignancy; some studies have also established SO2 as an independent biomarker of disease progression. Additionally, because cancerous …
Understanding The Role Of Arglu1 In Interferon Signaling Activation In Breast Cancer, Phuoc Nguyen
Understanding The Role Of Arglu1 In Interferon Signaling Activation In Breast Cancer, Phuoc Nguyen
Dissertations & Theses (Open Access)
In the U.S., the highest number of new cancer cases belongs to breast cancer in women, and this cancer also bears the second-highest death rate in women. Despite significant progress in breast cancer treatment that has been made in the past several decades, innovative and efficient therapies are still needed to eradicate this deadly disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in breast cancer treatment, IFN signaling induction is a …
Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi
Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi
Dissertations & Theses (Open Access)
Breast cancer brain metastases have remained one of the most intense challenges for precision cancer therapeutics, but current treatment options are limited and not curative. Recently, our lab reported that adoptive PTEN downregulation in metastatic breast tumor cells activates PI3K/NF-ƙB signaling and increases the secretion of the chemokine CCL2, which enhances the chemotaxis of CCR2+ myeloid cells, a major subpopulation of bone marrow-derived myeloid cells (BMDMs), from peripheral blood into the brain tumor microenvironment (TME), eventually promoting brain metastasis outgrowth by driving immune suppression. Here, in this project we have been aiming to develop effective therapies by immune-modulating the …
Combined Inhibition Of Ddr1 And Cdk4/6 Induces Synergistic Effects In Er-Positive, Her2-Negative Breast Cancer With Pik3ca/Akt1 Mutations, Maryam Shariati, Maryam Shariati
Combined Inhibition Of Ddr1 And Cdk4/6 Induces Synergistic Effects In Er-Positive, Her2-Negative Breast Cancer With Pik3ca/Akt1 Mutations, Maryam Shariati, Maryam Shariati
Dissertations & Theses (Open Access)
COMBINED INHIBITION OF DDR1 AND CDK4/6 INDUCES SYNERGISTIC EFFECTS IN ER-POSITIVE, HER2-NEGATIVE BREAST CANCER WITH PIK3CA/AKT1 MUTATIONS
Maryam Shariati, M.S. Advisory Professor: Funda Meric-Bernstam, M.D.
Molecular alterations in the phosphatidylinositol 3‑kinase (PI3K)/ serine/threonine protein kinase B (AKT) signaling pathway occur frequently in estrogen receptor–positive (ER-positive) breast tumors. Patients with ER-positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer are often treated with cyclin-dependent kinase (CDK4/6) inhibitors such as palbociclib in combination with endocrine therapy. Although this is a very effective regimen, disease progression ultimately occurs in most patients. Further, the modulators of palbociclib sensitivity remain unclear. The purpose …
Bst2 Isoforms: Distribution And Potential Use In Cancer Therapeutics, Ahmed Muhsin
Bst2 Isoforms: Distribution And Potential Use In Cancer Therapeutics, Ahmed Muhsin
Dissertations & Theses (Open Access)
Identifying a cancer-specific cellular target is one of the key factors that can pave a “bench to the bedside” path of a target therapy. Bone marrow stromal cell antigen 2 (BST2) is a raft-associated type II transmembrane protein with an unusual topology. Analyses showed a variable degree of BST2 expression in most organs. Two research groups identified different BST2 isoforms of BST2 generated by posttranscriptional modification. In this research, I studied the long BST2 isoform’s distribution in breast tissue and B cell lines using the novel monoclonal antibody (MAb) LA5, an anti-BST2-long MAb. This approach revealed the expression of the …
Functional Heterogeneity And Metabolic Adaptation Of Fibroblasts In Cancer, Lisa Becker
Functional Heterogeneity And Metabolic Adaptation Of Fibroblasts In Cancer, Lisa Becker
Dissertations & Theses (Open Access)
The tumor microenvironment is comprised of a multitude of cell types producing a milieu of cytokines, growth factors an extracellular matrix. Together, this intricate network of cells plays highly critical roles in determining a tumor’s potential to progress and metastasize. As the predominant cell types in the tumor microenvironment, cancer-associated fibroblasts (CAFs) are a key component in the regulation of tumor development and progression, but their exact functions in tumorigenesis remain poorly understood. This is partly due to the considerable heterogeneity amongst these cells, which confounds the characterization of their roles within the tumor microenvironment. Nevertheless, recent studies have provided …
Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria
Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria
Dissertations & Theses (Open Access)
GCN5 is the catalytic subunit in the acetyltransferase module of SAGA and ATAC, multiprotein complexes involved in the modification of histone and nonhistone proteins. GCN5 is most recognized as a co-activator of gene transcription. The SAGA complex is recruited to chromatin by transcription factors such as MYC and E2F1 where GCN5 acetylates H3K9 leading to a more open and accessible chromatin structure. Previous research has demonstrated that GCN5 also acetylates MYC, a protein that amplifies the expression of cancer-promoting genes and is frequently dysregulated in cancer, increasing its stability. Our lab has found there is a significant overlap in the …
Development Of Automated Radiotherapy Treatment Planning For Cervical And Breast Cancer For Resource-Constrained Clinics, Kelly Kisling
Development Of Automated Radiotherapy Treatment Planning For Cervical And Breast Cancer For Resource-Constrained Clinics, Kelly Kisling
Dissertations & Theses (Open Access)
Globally, cancer rates are on the rise, especially in low- and middle-income countries (LMICs). However, many of these countries lack access to radiotherapy, which is due in part to a substantial shortage of the staff necessary to deliver safe and effective radiotherapy. This staff shortage could be mitigated by the automation of the radiation treatment planning process. To this end, we developed automated planning for cervical and postmastectomy breast cancer radiotherapy, the two most common types of cancer in women in many LMICs.
For radiotherapy of cervical cancer in resource-constrained clinics, the recommended treatment technique is a four-field box. We …
The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le
The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le
Dissertations & Theses (Open Access)
Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …
Investigating Invasion In Ductal Carcinoma In Situ With Topographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent
Investigating Invasion In Ductal Carcinoma In Situ With Topographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent
Dissertations & Theses (Open Access)
Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …
Genomic Evolution Of Chemoresistance In Triple-Negative Breast Cancer Delineated By Single Cell Sequencing, Charissa Kim
Genomic Evolution Of Chemoresistance In Triple-Negative Breast Cancer Delineated By Single Cell Sequencing, Charissa Kim
Dissertations & Theses (Open Access)
Triple-negative breast cancer (TNBC) is an aggressive subtype that displays extensive intratumor heterogeneity and frequently (46%) develops resistance to neoadjuvant chemotherapy (NAC). Currently, the genomic basis of chemoresistance remains poorly understood. An important question is whether resistance to chemotherapy is driven by the selection of rare pre-existing subclones with genomic mutations and transcriptional programs that confer resistance to chemotherapy (adaptive resistance) or by the spontaneous induction of new mutations and expression changes that confer a resistant phenotype (acquired resistance). To investigate this question we applied single cell DNA and RNA sequencing methods and deep-exome sequencing to longitudinal time-point samples collected …
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Dissertations & Theses (Open Access)
Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …
Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu
Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu
Dissertations & Theses (Open Access)
Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …
Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez
Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez
Dissertations & Theses (Open Access)
Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found …
Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi
Potentially Inappropriate Medication Use In Older Patient With Breast And Colorectal Cancer, Meghan S. Karuturi
Dissertations & Theses (Open Access)
Our objective was to determine predictors of potentially inappropriate medication (PIM) use and its impact on outcomes (including ER visits, hospitalization, all cause death, and composite of three) in breast and colorectal cancer patients receiving chemotherapy. We used data from the SEER database linked to Medicare claims. Our cohort included patients ≥ 66 years diagnosed with of Stage II/III breast or colorectal cancer between 7/1/2007-12/31/2009. Baseline PIM was defined using the Drugs to Avoid in the Elderly list (DAE) or Beers criteria. Univariate and multivariable logistic regression were used to determine the associations of baseline PIMs with different covariates. Event-free …
The Role Of Amp-Activated Protein Kinase (Ampk) In Tumorigenesis, Fei Han
The Role Of Amp-Activated Protein Kinase (Ampk) In Tumorigenesis, Fei Han
Dissertations & Theses (Open Access)
AMPK plays a central role in controlling cellular and whole body energy level. Increasing studies have also discovered the diverse function of AMPK in cancer, such as autophagy and mitochondria biogenesis. However, how AMPK promotes cancer progression is still not clear. Here, we show that AMPK is essential for EGF-induced Akt activation, Glut1 expression, and glucose uptake. AMPK is also required for various stresses induced Akt activation and promote cell survival, including hypoxia and glucose deprivation. In addition, we found glucose deprivation-induced VEGF expression and secretion is also depend on AMPK, which may contribute to angiogenesis of surrounding endothelial cell …
Targeting Oncogenic Mirnas With Small Molecules For Breast Cancer Therapy, Paloma Del C. Monroig
Targeting Oncogenic Mirnas With Small Molecules For Breast Cancer Therapy, Paloma Del C. Monroig
Dissertations & Theses (Open Access)
The crucial role of microRNAs (miRNAs) in cancer pathobiology has driven the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, there is a need to develop screening strategies that can target tumors in a specific way. Small molecule inhibitors represent an attractive approach to pursue this. However, the absence of molecular structures for most of the miRNAs makes it very difficult to predict which inhibitors can bind to them. Herein we designed a strategy to screen for small molecules by assesing whether they could directly bind/ interact with miR-10b/miR-21. As part of our …
Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith
Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith
Dissertations & Theses (Open Access)
Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – …
Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff
Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff
Dissertations & Theses (Open Access)
Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …
Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes
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 …
Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou
Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou
Dissertations & Theses (Open Access)
Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death, including breast cancer. Our previous finding in patients showed that anti-insulin resistance treatments are associated with improved HER2+ breast cancer survival of diabetic women. However, there were no transgenic mouse models to study the correlation and explain the detailed mechanism. We generated a mouse model of HER2+ breast cancer with DM2 by crossing leptin receptor point mutation (Lepr db/+) and MMTV-ErbB2 (neu) mice. The MMTV-ErbB2/Lepr db/db mice had a poor survival rate compared …
The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering
The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering
Dissertations & Theses (Open Access)
MicroRNA (miRNA) are small, non-coding RNAs that affect gene expression through degradation of complementary mRNA targets or inhibition of translation. As they affect approximately 50% of all cellular processes, miRNA are tightly regulated by the cell through transcriptional and post-transcriptional mechanisms. Transcribed miRNA are capped and polyadenylated (referred to as pri-miRNA) which are cleaved by Drosha and DGCR8 to generate 60-90 nucleotide precursor miRNA. The precursors are cleaved again by Dicer and loaded into the RNA-induced silencing complex (RISC) of which Argonaute 2 is the functional component. Many of the proteins involved in miRNA biogenesis share a common role in …
Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, Sumaiyah Rehman
Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, Sumaiyah Rehman
Dissertations & Theses (Open Access)
Signaling pathways that play critical roles in organ development are often aberrantly regulated during cancer initiation and progression. 14-3-3z is overexpressed in more than 40% of breast cancers and is associated with poor patient prognosis. Therefore, the function of 14-3-3z in cancer and normal mammary gland development was investigated utilizing multiple in vivo and in vitro approaches. 14-3-3z is a chaperone protein that interacts with a multitude of oncogenes and tumor suppressor genes, thereby functioning as a critical node in multiple oncogenic signaling networks. Mammary gland-specific 14-3-3z transgenic mouse models showed that 14-3-3z overexpression was sufficient to induce mammary tumorigenesis. …
Symptoms In Early And Long-Term Breast Cancer Survivors Who Have Completed Primary Therapy, Faith Strunk
Symptoms In Early And Long-Term Breast Cancer Survivors Who Have Completed Primary Therapy, Faith Strunk
Dissertations & Theses (Open Access)
Background
Many breast cancer survivors continue to have single or multiple symptoms after they have completed primary cancer therapy. The quantifiable, subjective experience of multiple symptoms and their impact is defined as symptom burden. Previous research has focused on symptoms during primary therapy or shortly after completion of treatment.
Objectives
Our study objectives were to determine whether symptom burden differed according to survivor status (early as opposed to long-term survival) and/or use of endocrine or hormonal adjuvant therapy. We hypothesized that there would be no difference in the symptoms expressed among early- and long-term survivors.
Methods
In this cross-sectional study, …
Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff
Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff
Dissertations & Theses (Open Access)
Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been …
Interaction Between Brk And Her2 In Breast Cancer, Midan Ai
Interaction Between Brk And Her2 In Breast Cancer, Midan Ai
Dissertations & Theses (Open Access)
INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER
Midan Ai, Ph.D.
Supervisory Professor: Zhen Fan, M.D.
Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast cancer. The mechanism …
The Role Of Type I Insulin-Like Growth Factor Receptor Signaling In Breast Cancer Brain Metastasis, Sandra M. Saldana
The Role Of Type I Insulin-Like Growth Factor Receptor Signaling In Breast Cancer Brain Metastasis, Sandra M. Saldana
Dissertations & Theses (Open Access)
Brain metastasis is a common cause of mortality in cancer patients. Approximately 20-30% of breast cancer patients acquire brain metastasis, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF- IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that the IGF-IR signaling axis is constitutively active in brain-seeking sublines of breast cancer cells, driving an increase in in vitro metastatic properties. We demonstrate that IGF-IR signaling is activated in an autocrine manner …
Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf
Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf
Dissertations & Theses (Open Access)
Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …
Regulation Of Net1a Subcellular Localization By The Small Gtpase Rac1, Christopher A. Morris
Regulation Of Net1a Subcellular Localization By The Small Gtpase Rac1, Christopher A. Morris
Dissertations & Theses (Open Access)
Activation of Rho family small G proteins is thought to be a critical event in breast cancer development and metastatic progression. Rho protein activation is stimulated by a family of enzymes known as guanine nucleotide exchange factors (Rho GEFs). The neuroepithelioma transforming gene 1 (Net1) is a Rho GEF specific for the RhoA subfamily that is overexpressed in primary breast tumors and breast cancer cell lines. Net1 isoform expression is also required for migration and invasion of breast cancer cells in vitro. These data indicate that Net1 may be a critical regulator of metastatic progression in breast cancer. Net1 activity …