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Cancer Biology

2013

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Articles 1 - 23 of 23

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li Dec 2013

New Insights Into The Roles Of Human Dna Damage Checkpoint Protein Atr In The Regulation Of Nucleotide Excision Repair And Dna Damage-Induced Cell Death, Zhengke Li

Electronic Theses and Dissertations

Integrity of the human genome is frequently threatened by endogenous and exogenous DNA damaging reagents that may lead to genome instability and cancer. Cells have evolved multiple mechanisms to repair DNA damage or to eliminate the damaged cells beyond repair and to prevent diverse diseases. Among these are ataxia telangiectasia and Rad3-related (ATR)-mediated DNA damage checkpoint and nucleotide excision repair (NER) that are the major pathways by which cells handle ultraviolet C (UV-C)- or other exogenous genotoxin-induced bulky DNA damage. However, it is unclear how these 2 pathways may be coordinated. In this study we show that ATR physically ...


Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari Oct 2013

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Open Dartmouth: Faculty Open Access Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using ...


Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs Oct 2013

Identification Of Set1 Target Genes, William Beyer, Scott D. Briggs

The Summer Undergraduate Research Fellowship (SURF) Symposium

The Set1 complex, a histone methyltransferase complex found in S. cerevisiae (budding yeast), is the only histone methyltransferase responsible for catalyzing methylation of histone H3 at Lysine 4. It possesses homologues in other species, humans included. While yeast only have the Set1 complex, the human homologues of the yeast Set1 complex include mixed-lineage leukemia family (MLL1-4), Set1 A, Set1 B, among others. MLL1-4 has been shown to play a role in transcription, cell type specification, and the development of leukemia. One application of characterizing the role of a protein is that the information gained can provide insight into the function ...


Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio Oct 2013

Id2 Complexes With The Snag Domain Of Snai1 Inhibiting Snai1-Mediated Repression Of Integrin Beta4, Cheng Chang, Xiaofang Yang, Bryan Pursell, Arthur M. Mercurio

Cancer Biology Publications and Presentations

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains ...


Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou Aug 2013

Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou

Theses and Dissertations

Estrogen plays essential roles in the growth, development, and homeostasis of a number of tissues, and can also be linked to the growth of breast cancer. The biological activities of estrogen are mediated by estrogen receptors (ERs) ERá and ERâ, and also orphan G-protein-coupled receptor 30 (GPR30). In order to identify novel proteins that are involved in ER-mediated actions of estrogen, we used mass spectrometry-based quantitative proteomic methods to systematically profile global protein expression in responses to E2 (17â-estradiol) stimulation in human breast cancer cell, and identify and characterize cellular novel proteins that are associated with ERs in breast cancer ...


Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja Aug 2013

Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja

UT GSBS Dissertations and Theses (Open Access)

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is common; thus, it is essential to improve the effectiveness and reduce toxicity of current treatments. Proteins in the Src/Jak/STAT pathway represent potential therapeutic targets, as this pathway is hyperactive in HNSCC and it has roles in cell migration, metastasis, proliferation, survival, and angiogenesis. During short-term Src inhibition, Janus kinase (Jak) 2, and signal transducer and activator of transcription (STAT) 3 and STAT5 are dephosphorylated and inactivated. Following sustained Src inhibition, STAT5 remains inactive, but Jak2 and STAT3 are reactivated following their early inhibition. To further characterize the mechanism ...


Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri Jul 2013

Characterizing The Role Of The Retinoblastoma Protein Lxcxe Binding Cleft In Cellular Senescence And Tumor Suppression, Srikanth Talluri

Electronic Thesis and Dissertation Repository

The Retinoblastoma protein (pRB) is a key regulator of the cell cycle and is functionally inactivated in most cancers. pRB has been proposed to utilize simultaneous interactions with E2F transcription factors and chromatin regulatory proteins to repress transcription and block cell cycle progression. The goal of this study is to characterize the physiological role of pRB interactions with chromatin regulatory proteins. I used gene targeted mice carrying point mutations in the murine Rb1 gene (Rb1∆L) that specifically disrupt pRB’s LXCXE binding cleft, and thereby its ability to interact with chromatin regulatory proteins while leaving its ability to bind ...


Purification And Characterization Of Oxidation-Resistant Ribonuclease Inhibitor Variants, Alec W. Uebersohn May 2013

Purification And Characterization Of Oxidation-Resistant Ribonuclease Inhibitor Variants, Alec W. Uebersohn

Lawrence University Honors Projects

Ribonuclease inhibitor (RI) is an intracellular mammalian protein which binds vertebrate-specific ribonucleases; this interaction is one of the tightest non-covalent interactions yet discovered. The biological activity of RI is poorly understood, but it is thought to regulate the biological functions of ribonucleases, which include initiating blood vessel growth, maintaining neuron viability, attacking pathogens, and mediating cell stress responses. RI is also involved in pathways unrelated to ribonucleases, including interactions with Drosha and PTEN, an anti-tumor protein.

One of the defining characteristics of RI is its oxidation sensitivity, a result of its unusually high cysteine content. The oxidation of RI is ...


Systematic Analysis Of Residues In Conserved Region 3 Of The Human Papillomavirus 16 E7 Oncoprotein, Biljana Todorovic May 2013

Systematic Analysis Of Residues In Conserved Region 3 Of The Human Papillomavirus 16 E7 Oncoprotein, Biljana Todorovic

Electronic Thesis and Dissertation Repository

Although remarkable biological diversity is exhibited by viruses, as obligate intracellular parasites, they rely on host cell functions. As such, viruses typically must overcome a set of host barriers that prevent infection. For human papillomaviruses (HPV) one of these barriers is the state of terminal differentiation of the host cell. For that purpose HPVs encode two major oncoproteins, E6 and E7, which combine their efforts to effectively uncouple cellular differentiation from the cell cycle arrest. The E7 proteins have no intrinsic enzymatic activity or DNA binding ability, but they bind and manipulate numerous host proteins. E7 is a modular oncoprotein ...


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre May 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Alfred M Legendre DVM, MS, DACVIM

No abstract provided.


Molecular Mechanisms Of Fsh Muscular Dystrophy Pathogenesis, Peter L. Jones, Takako I. Jones May 2013

Molecular Mechanisms Of Fsh Muscular Dystrophy Pathogenesis, Peter L. Jones, Takako I. Jones

UMass Center for Clinical and Translational Science Research Retreat

Discussion of a new research initiative at UMass Medical School focused on the pathogenesis of Facioscapulohumeral Muscular Dystrophy (FSHD) and efforts towards diagnostics and therapeutics. This presentation is part of the retreat mini-symposium entitled: Neuromuscular Diseases: Pathogenesis and the Road to Therapeutics.


Regulation Of Androgen Receptor Co-Regulators By Activation Of The Cxcl12/Cxcr4 Axis: A Microarray And Proteomics Approach, Sathish Kasina, Lesa Begley, Henriette Remmer, Jill A. Macoska May 2013

Regulation Of Androgen Receptor Co-Regulators By Activation Of The Cxcl12/Cxcr4 Axis: A Microarray And Proteomics Approach, Sathish Kasina, Lesa Begley, Henriette Remmer, Jill A. Macoska

UMass Center for Clinical and Translational Science Research Retreat

Background: Activation of the CXCL12/CXCR4 axis is known to stimulate androgen-independent activation of the androgen receptor (AR) in the LNCaP prostate cancer cell line. In the present study, the CXCL12-stimulated expression profile of androgen responsive genes (ARGs) and AR:co-regulator protein:protein interactions has been identified by microarray and proteomic analysis, respectively.

Methods: To directly identify proteins that interacted with the AR in response to CXCL12 stimulation, LNCaP cells treated with CXCL12 were subjected to a total proteomics analysis after co-immunoprecipitation (co-IP) with anti-AR antibody. AR- interacting proteins from co-IP were pre-fractionated by SDS-PAGE, in-gel trypsin digested, and analyzed ...


Glyconanoparticle Uptake Profile In Lung Carcinoma Cells, Kalana W. Jayawardana, H. Surangi N. Jayawardena, Thareendra De Zoysa, Mingdi Yan May 2013

Glyconanoparticle Uptake Profile In Lung Carcinoma Cells, Kalana W. Jayawardana, H. Surangi N. Jayawardena, Thareendra De Zoysa, Mingdi Yan

UMass Center for Clinical and Translational Science Research Retreat

Non-small cell lung carcinoma (NSCLC) is responsible for nearly 85% of lung cancer, and early diagnosis and treatment of lung cancer can circumvent possible death. We focus on glyconanoparticles with a magnetic or a fluorescent core that act as multivalent glyco-scaffold to study cell surface interaction and internalization. The glyconanoparticles were synthesized by conjugating various carbohydrates on magnetic nanoparticles and fluorescent silica nanoparticles by a photocoupling technique developed in our laboratory. The size of nanoparticles used varies from 6 nm to 60 nm. The resulting glyconanoparticles were treated with human adenocarcinoma non-small lung epithelial cells (A549) and the primary small ...


Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White May 2013

Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White

UT GSBS Dissertations and Theses (Open Access)

The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce ...


Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett Apr 2013

Molecular Imaging Of Cyclooxygenase-2 In Canine Transitional Cell Carcinomas In Vitro And In Vivo, Maria Cekanova, M Uddin, Joseph Bartges, Amanda Callens, Kusum Rathore, Alfred Legendre, L Wright, L Marnett

Maria Cekanova MS, RNDr, PhD

The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by 70% (P < 0.005) when pretreated with the COX-2 selective inhibitor, celecoxib (10 mg/kg), 4 hours before intravenous administration of fluorocoxib A (1 mg/kg). Fluorocoxib A was taken up by COX-2-expressing tumors but not by COX-2-negative human UMUC-3 xenograft tumors. UMUC-3 xenograft tumors with no expression of COX-2 showed no uptake of fluorocoxib A. In addition, fluorocoxib A uptake was evaluated in five dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo.


Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa Mar 2013

Modulation Of Adipose Tissue Inflammation By Bioactive Food Compounds, N. Siriwardhana, N. Kalupahana, Maria Cekanova, M. Lemieux, B. Greer, N, Moustaid-Moussa

Maria Cekanova MS, RNDr, PhD

Adipose tissue has an important endocrine function in the regulation of whole-body metabolism. Obesity leads to a chronic low-grade inflammation of the adipose tissue, which disrupts this endocrine function and results in metabolic derangements, such as type-2 diabetes. Dietary bioactive compounds, such as polyphenols and certain fatty acids, are known to suppress both systemic and adipose tissue inflammation and have the potential to improve these obesity-associated metabolic disorders. Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating ...


Investigating The Interplay Between Protein Kinases And Caspases, Jacob P. Turowec Mar 2013

Investigating The Interplay Between Protein Kinases And Caspases, Jacob P. Turowec

Electronic Thesis and Dissertation Repository

The balance between cell survival and death is a crucial process in human development and tissue homeostasis, but is also misregulated in disease. In large part, apoptosis is controlled by caspases, a hierarchical series of cysteine aspartic acid proteases that demolish the cell by cleaving key structural and enzymatic proteins, but emerging paradigms have highlighted the ability of kinases to regulate caspase activity. One way in which kinases can control the progression of apoptosis is through phosphorylation of caspase substrates, which acts to prevent caspase cleavage of that target.

In this thesis, we develop new strategies to study this regulatory ...


De-Regulation Of Jnk And Jak/Stat Signaling In Escrt-Ii Mutant Tissues Cooperatively Contributes To Neoplastic Tumorigenesis, Sarah E. Woodfield, Hillary K. Graves, Jacob Hernandez, Andreas Bergmann Feb 2013

De-Regulation Of Jnk And Jak/Stat Signaling In Escrt-Ii Mutant Tissues Cooperatively Contributes To Neoplastic Tumorigenesis, Sarah E. Woodfield, Hillary K. Graves, Jacob Hernandez, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

Multiple genes involved in endocytosis and endosomal protein trafficking in Drosophila have been shown to function as neoplastic tumor suppressor genes (nTSGs), including Endosomal Sorting Complex Required for Transport-II (ESCRT-II) components vacuolar protein sorting 22 (vps22), vps25, and vps36. However, most studies of endocytic nTSGs have been done in mosaic tissues containing both mutant and non-mutant populations of cells, and interactions among mutant and non-mutant cells greatly influence the final phenotype. Thus, the true autonomous phenotype of tissues mutant for endocytic nTSGs remains unclear. Here, we show that tissues predominantly mutant for ESCRT-II components display characteristics of neoplastic transformation and ...


Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre Jan 2013

Neutron Radiography With Combined Computed Tomography: A Novel Tool For Cancer Diagnosis And Imaging (Abstract), Maria Cekanova, H Bilheux, Kusum Rathore, J Bilheux, L Walker, Robert Donnell, Alfred Legendre

Maria Cekanova MS, RNDr, PhD

No abstract provided.


Microfabricated Nanotopological Surfaces For Study Of Adhesion-Dependent Cell Mechanosensitivity, Weiqiang Chen, Yubing Sun, Jianping Fu Jan 2013

Microfabricated Nanotopological Surfaces For Study Of Adhesion-Dependent Cell Mechanosensitivity, Weiqiang Chen, Yubing Sun, Jianping Fu

Weiqiang Chen

Cells exhibit high sensitivity and diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery. A simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces by using photolithography and reactive ion etching is reported. It is demonstrated that local nanoroughness as a biophysical cue could regulate a diverse array of NIH/3T3 fi broblast behaviors, including cell morphology, adhesion, proliferation, migration, and cytoskeleton contractility. The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo ...


Omega-3 Fatty Acids As Therapeutic Options For The Treatment Of B-Cell Chronic Lymphocytic Leukemia, Johannes Francois Fahrmann Jan 2013

Omega-3 Fatty Acids As Therapeutic Options For The Treatment Of B-Cell Chronic Lymphocytic Leukemia, Johannes Francois Fahrmann

Theses, Dissertations and Capstones

B-cell chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the western world. CLL is often diagnosed in the asymptomatic (early-stage) stages. However, approximately 50% of these patients will progress to advanced, symptomatic disease and require therapy. Current treatment options are limited due to progressive drug resistance and severe drug-induced toxicities which are often too toxic for the elderly or those with co-morbidities. Therefore, a non-toxic therapeutic intervention that could slow the progression of asymptomatic CLL to symptomatic CLL or enhance the effects of actively used chemo-therapeutic drugs in patients who require therapy would be clinically ...


Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang Dec 2012

Mesenchymal And Stem-Like Properties Targeted In Suppression Of Chronically-Induced Breast Cell Carcinogenesis, Kusum Rathore, Hwa-Chain Wang

Hwa-Chain Robert Wang

No abstract provided.


Rab5 Function In Breast Cancer Cells, Nicole Porther, M Alejandro Barbieri Dec 2012

Rab5 Function In Breast Cancer Cells, Nicole Porther, M Alejandro Barbieri

Nicole Porther

Metastasis is characterized pathologically by cell invasion, proliferation, migration and angiogenesis. Growth factors, which include epithelial growth factor (EGF), insulin growth factors I and II (IGFI and IGFII); have been associated with most if not all of the features of metastasis.  Our study has highlighted the possible role growth factors may have in mediating cancer metastasis via Rab GTPses.  We determined that the invasive and migratory properties of breast cancer cells were abrogated in cell lines that only expressed the inactive (GDP-bound) form of Rab 5 irrespective of growth factor stimulation. Breast cancer cell lines expressing the wild type and ...