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Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak 2018 The University of Akron

Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak

Honors Research Projects

Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as ...


Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill 2017 Australian National University

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct ...


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 ...


Role Of Peptidylarginine Deiminase 2 (Pad2) In Mammary Carcinoma Cell Migration, Sachi Horibata, Katherine E. Rogers, David Sadegh, Lynne J. Anguish, John L. McElwee, Pragya Shah, Paul R. Thompson, Scott A. Coonrod 2017 Cornell University

Role Of Peptidylarginine Deiminase 2 (Pad2) In Mammary Carcinoma Cell Migration, Sachi Horibata, Katherine E. Rogers, David Sadegh, Lynne J. Anguish, John L. Mcelwee, Pragya Shah, Paul R. Thompson, Scott A. Coonrod

Thompson Lab Publications

BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process.

METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes ...


Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis 2017 Clark Atlanta University

Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins ...


Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke 2017 Atlanta University Center

Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2 ...


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 ...


A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17 2017 Illinois Mathematics and Science Academy

A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17

Independent Study

Epithelial-Mesenchymal Transition (EMT) is a biological process utilized by epithelial cells to transform into motile mesenchymal cells, initiating metastasis in cancer. EMT is also utilized during development and wound healing [10]. This process allows for cancerous cells to detach themselves from their primary tumor and invade normal tissue in preferred organ sites, forming secondary tumors called metastases. Metastasis is very important in the progression of cancer in patients as it the process responsible for the mortality of patients through the collection of metastases that effect vital organs like the brain, lung, or immune system. The most common metastases for malignant ...


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 ...


Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano 2017 University of Massachusetts Medical School

Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano

UMass Metabolic Network Publications

Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators. Reduction in lipid synthesis lowers proliferation rates, which can be restored by palmitate supplementation. This work has established BRG1 as ...


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 ...


Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill 2017 Australian National University

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Faculty of Health Sciences & Medicine Publications

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct ...


Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey 2017 Maseno University

Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey

University of Massachusetts Medical School Faculty Publications

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep ...


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 ...


Coexpression Of Normally Incompatible Developmental Pathways In Retinoblastoma Genesis, Justina McEvoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer 2017 St. Jude Children's Research Hospital

Coexpression Of Normally Incompatible Developmental Pathways In Retinoblastoma Genesis, Justina Mcevoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer

Jeffrey Trimarchi

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are ...


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