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The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu 2017 The Graduate Center, City University of New York

The P53 Independent Functions Of Estrogen-Activated Mdm2 In Cell Signaling And Mammary Architecture, Nandini Kundu

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

Estrogen receptor positive (ER+) breast cancers often have MDM2 overexpression indicating a critical role for MDM2 in breast cancer tumorigenesis. The cancer genome atlas (TCGA) found that increased MDM2 expression is one of the four pathways that correlate with all breast cancer subtypes. MDM2 is mainly known as the negative regulator of wild type p53. However, aggressive breast cancers often have MDM2 overexpression and mutant p53 (mtp53). We previously reported that MDM2 provides an estrogen-mediated proliferative advantage to MCF-7 breast cancer cells (ER+, MDM2 overexpression, wild type p53), independent of wild type p53 in both 2D and 3D culture conditions ...


Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana 2017 Seton Hall University

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)2 has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)2 sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential ...


Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green 2017 University of Massachusetts Medical School

Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green

Senior Scholars Program

Background: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Since a significant portion of cases present with or progress to metastatic disease, furthering our understanding of metastasis is critical to develop better treatments. Epithelial cells maintain contact with the extracellular matrix (ECM) predominantly via integrin engagement, a process required for tissue integrity and barrier function. In non-transformed cells, loss of ECM adhesion promotes a specialized form of programmed cell death, anoikis. In order for efficient metastasis to occur, breast tumor cells must evade anoikis. miR-203, known to be down-regulated in several cancers, was found by our ...


Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

UT GSBS Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates ...


Mechanism Of Lck Activation In Driving Leukemia Cell Proliferation, Hannah E. Dobson 2017 University of Rhode Island

Mechanism Of Lck Activation In Driving Leukemia Cell Proliferation, Hannah E. Dobson

Senior Honors Projects

Leukemia is a type of cancer that develops in blood-forming tissues of the immune system. These tissues can include the bone marrow or sites within the lymphatic system such as the lymph nodes. Leukemia progresses from a mutational event within a white blood cell. Often this mutation alters the cell’s normal life cycle, resulting in uninhibited cell division and growth. With this uncontrolled cell proliferation, mutated white blood cells accumulate and begin interfering with the functioning of healthy cells.

Scientists are unsure of the exact mechanisms required for leukemia development. However, recently scientists identified four characteristic mutations in the ...


Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw 2017 University of Massachusetts Medical School

Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw

UMass Metabolic Network Publications

News on: Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition, by Hong et al. Oncotarget. 2017; 8:17610-27. doi: 10.18632/oncotarget.15381.


C-Myc’S Role On Methylation Of The Gata-2 Gene In Non-Small Cell Lung Carcinoma, Jonathan D. Hajduk 2017 Lynchburg College

C-Myc’S Role On Methylation Of The Gata-2 Gene In Non-Small Cell Lung Carcinoma, Jonathan D. Hajduk

Student Scholar Showcase

Lung cancer accounts for more deaths per year than any other form of cancer, resulting in a total of 158,000 deaths per year in the U.S. Non-small cell lung cancer (NSCLC) is diagnosed in greater than 224,000 Americans every year. Methylation and subsequent downregulation of certain genes has been directly linked to the uncontrolled growth of NSCLC cells. Natural killer (NK) cells are key innate immune cells responsible for apoptosis of cells with incorrect genetic code. It is believed that one component of uncontrolled NSCLC growth is due to the NK cells’ inability to detect errors within ...


Cancer As A Metabolic Disease, Javaria Haseeb 2017 Merrimack College

Cancer As A Metabolic Disease, Javaria Haseeb

Honors Senior Capstone Projects

Despite decades of intensive scientific and medical efforts to develop efficient and effective treatments for cancer, it remains one of the prime causes of death today. For example, in 2016, there will be an estimated 1,685,210 new cases of cancer and 595,690 deaths due to cancer in the United States alone (National Cancer Institute). Worldwide in 2012, there were an estimated 14 million new cases of cancer and 8.2 million deaths due to cancer. In order to come up with better methods of detection and more successful modes of treatment, it is crucial that scientists understand ...


Sumo-Targeted Ubiquitin Ligase (Stubl) Slx5 Regulates Proteolysis Of Centromeric Histone H3 Variant Cse4 And Prevents Its Mislocalization To Euchromatin, Kentaro Ohkuni, Yoshimitsu Takahashi, Alyona Flup, Josh La, Wei-Chun Au, Nagesh Pasupala, Ruben Levy-Meyers, Jack Warren, Alexander Strunnikov, Richard E. Baker, Oliver Kerscher, Kerry Bloom, Munira A. Basrai 2017 College of William and Mary

Sumo-Targeted Ubiquitin Ligase (Stubl) Slx5 Regulates Proteolysis Of Centromeric Histone H3 Variant Cse4 And Prevents Its Mislocalization To Euchromatin, Kentaro Ohkuni, Yoshimitsu Takahashi, Alyona Flup, Josh La, Wei-Chun Au, Nagesh Pasupala, Ruben Levy-Meyers, Jack Warren, Alexander Strunnikov, Richard E. Baker, Oliver Kerscher, Kerry Bloom, Munira A. Basrai

Oliver Kerscher

Centromeric histone H3, CENP-ACse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-ACse4 restricts its localization to centromeres. Mislocalization of CENP-ACse4 is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and ...


The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia da Costa 2017 George Washington University

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these ...


Metastatic Biomarkers In Synovial Sarcoma, Rosalia de Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi 2017 Loma Linda University

Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi

Library Articles and Research

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of ...


Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows 2017 Oregon State University

Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows

Biomedical Engineering Western Regional Conference

No abstract provided.


Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda 2017 The University of Western Ontario

Mt1-Mmp Mediates The Migratory And Tumourigenic Potential Of Breast Cancer Cells Via Non-Proteolytic Mechanisms, Mario Cepeda

Electronic Thesis and Dissertation Repository

Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that affects cell function via proteolytic and non-proteolytic mechanisms such as promoting degradation of the extracellular matrix (ECM) or augmentation of cell migration and viability, respectively. MT1-MMP has been implicated in metastatic progression ostensibly due to its ability to degrade ECM components and to allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) that inhibit substrate catalysis as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by ...


Melanoma Mystery, Roger J. Davis 2017 University of Massachusetts Medical School

Melanoma Mystery, Roger J. Davis

Davis Lab

Biological variability has confounded efforts to confirm the role of PREX2 mutations in melanoma.


Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar 2017 University of Kentucky

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings ...


Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith 2017 Old Dominion University

Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived ...


Press-Pulse: A Novel Therapeutic Strategy For The Metabolic Management Of Cancer, Thomas Seyfried, George Yu, Joseph Maroon, Dominic D'Agostino 2017 George Washington University

Press-Pulse: A Novel Therapeutic Strategy For The Metabolic Management Of Cancer, Thomas Seyfried, George Yu, Joseph Maroon, Dominic D'Agostino

Urology Faculty Publications

Background

A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of “Press-Pulse” disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred.

Methods

This general concept can be applied to the management of cancer by creating chronic metabolic stresses on tumor cell energy metabolism (press disturbance ...


The E. Coli Protein Ybgl: A Novel Dna Repair Enzyme?, Mason H. Conen, Brooke D. Martin, Kent Sugden, Savannah Whitfield 2017 University of Montana, Missoula

The E. Coli Protein Ybgl: A Novel Dna Repair Enzyme?, Mason H. Conen, Brooke D. Martin, Kent Sugden, Savannah Whitfield

Undergraduate Theses and Professional Papers

Cr(V) is a carcinogen that oxidizes guanine aggressively to form spiroiminodihydantion (Sp) and guanidinohydantoin (Gh), both of which contain an unusual hydantoin moiety that cause G→T transversion mutations at a high rate. Endonuclease VIII (nei) can recognize and excise these oxidation products from DNA and is translated as one of five protein products of the Nei operon in Escherichia coli (E. coli). However, the functions of the other four proteins remain unknown. To address this gap in knowledge, we focused on one of the four that immediately precedes nei, the ybgL protein. Previous work by our group has ...


Homothorax Is A Modifier Of Radiation Sensitivity In Drosophila Melanogaster Bantam Mutants, Geoffrey Meyerhof 2017 University of Colorado, Boulder

Homothorax Is A Modifier Of Radiation Sensitivity In Drosophila Melanogaster Bantam Mutants, Geoffrey Meyerhof

Undergraduate Honors Theses

Radiation resistance in human cancers represents a massive impediment for successful tumor treatment. The fruit fly Drosophila melanogaster is an excellent model for human radiation resistance because of its largely conserved apoptotic pathways and malleable genome. This thesis investigates the genetic regulatory mechanisms for bantam (ban), an anti-apoptotic microRNA. To first identify genes that interact with ban, a forward genetic screen was conducted. This screen looked for genes that yielded radiation dependent pupal lethality in a ban deficient background. From this screen the transcription factor, homothorax, was identified as displaying radiation dependent synthetic lethality with ban. To investigate the mechanism ...


The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham 2017 University of Colorado, Boulder

The Association Of Dcc Mrna Alternative Splicing With Colorectal Cancer, Natalie Graham

Undergraduate Honors Theses

In as many as 70% of colorectal cancer cell (CRC) lines, there is a deletion of a chromosomal region, 18q21, which contains the Deleted in Colorectal Carcinoma (DCC) gene (Mehlen & Fearon, 2004). In adult cells, this single transmembrane receptor plays a role in both cell proliferation and cell death, thereby making it a promising candidate gene for the pathogenesis of colorectal cancer. It has been observed that alternative splicing of the DCC can affect its activity and that alternative splicing of DCC can be disrupted in cancer (Leggere et al., 2016; Reale et al., 1994). In this experiment, we sought to determine the association of alternative splicing of the DCC with colorectal cancer in cells without the deletion of the 18q21 region. By extracting RNA from 35 CRC cell lines and performing RT-PCR, we observed levels of the two DCC isoforms compared to normal adult colon cells. In this way, we determined that 29 of 35 CRC cell lines had altered ...


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