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Taking A Cat Map: Genome Analysis By Supercomputer, Jose V. Lopez 2016 National Cancer Institute

Taking A Cat Map: Genome Analysis By Supercomputer, Jose V. Lopez

Jose Lopez

No abstract provided.


Semaphorin3a Increases Focal Adhesion Formation To Shift The Relationship Between Cell Migration And Substratum Concentration Through A Rock-Dependent Mechanism, Frances V. Compere, Scott Gehler 2016 Augustana College, Rock Island Illinois

Semaphorin3a Increases Focal Adhesion Formation To Shift The Relationship Between Cell Migration And Substratum Concentration Through A Rock-Dependent Mechanism, Frances V. Compere, Scott Gehler

Celebration of Learning

Cell migration is essential for many life processes, including wound healing, embryonic development and cancer metastasis. Cells move across a surface by interacting and forming adhesions with the molecules in their environment, specifically the extracellular matrix. Past studies have shown that there is an optimal level of cell-substratum adhesive strength that allows for the most cell migration and spreading (DiMilla et al., 1993; Gaudet et al., 2003). The mechanism by which this works is not well understood, however. Semaphorin 3A (Sema3A) has been shown to increase the expression of integrin receptors, which help mediate the formation of the adhesions between ...


Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill 2016 California State University - San Bernardino

Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill

Electronic Theses, Projects, and Dissertations

Ovarian cancer is the fifth leading cause of cancer death in women between the ages of 35 and 74. With 22 thousand new cases and 15 thousand deaths annually ovarian cancer is among the most deadly cancers with a death to incidence ratio of 68%. With 70% of cases High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer and causes 90% of ovarian cancer deaths. 80% of patients have reoccurrence within five years and only 15-30% of patients with recurrent metastatic ovarian cancer respond to current therapies, chemotherapy and surgery. One reason for the high ...


Explicitly Separating Growth And Motility In A Glioblastoma Tumor Model, Tracy Stepien, Erica Rutter, Meng Fan, Yang Kuang 2016 Arizona State University

Explicitly Separating Growth And Motility In A Glioblastoma Tumor Model, Tracy Stepien, Erica Rutter, Meng Fan, Yang Kuang

Biology and Medicine Through Mathematics Conference

No abstract provided.


Analysis Of A Novel Nonsense Mutation Of Androgen Receptor Gene In Castration-Resistant Prostate Cancer, Dong Han, Kevin Valencia, Shuai Gao, Changmeng Cai 2016 University of Massachusetts Boston

Analysis Of A Novel Nonsense Mutation Of Androgen Receptor Gene In Castration-Resistant Prostate Cancer, Dong Han, Kevin Valencia, Shuai Gao, Changmeng Cai

UMass Center for Clinical and Translational Science Research Retreat

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer mortality in American men. The standard treatment for PCa is androgen deprivation therapy (ADT) that blocks transcriptional activity of androgen receptor, but ADT invariably leads to the development of castration-resistant form of PCa (CRPC) with restored activity of AR. CRPC can be further treated with more intensive ADTs, including CYP17-inhibitors to block intratumoral androgen synthesis and more potent AR antagonist (enzalutamide). Most CRPC patients still relapse after a year of treatment and AR activity appears to be restored again. By analyzing the tumor mRNA from a CRPC patient biopsy ...


Targeted Combination Treatment For Glioblastoma Multiforme (Gbm) Using Polymeric Nanoparticle, Praveena Velpurisiva, Michael Tilton, Brandon Piel, Prakash Rai 2016 University of Massachusetts Lowell

Targeted Combination Treatment For Glioblastoma Multiforme (Gbm) Using Polymeric Nanoparticle, Praveena Velpurisiva, Michael Tilton, Brandon Piel, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Glioblastoma Multiforme (GBM) is an aggressive cancer that originates from astrocytes and spreads to spinal cord and other parts of the brain. Increase in replication of glial cells leads to advantageous mutations in the tumor. In 2015 about 15,320 deaths were reported due to GBM. Five-year survival is less than 5% making GBM a dreadful cancer. Current treatment involves complex invasive surgery, followed by chemotherapy and radiation. There is a desperate unmet need for a targeted treatment of GBM with minimum damage to the surrounding normal tissue. Combination treatments are increasingly being used to target multiple hallmarks of cancer ...


Implantable Microenvironments To Capture Stable-To- Aggressive Tumor Transition, Ryan Carpenter, Jungwoo Lee 2016 University of Massachusetts Amherst

Implantable Microenvironments To Capture Stable-To- Aggressive Tumor Transition, Ryan Carpenter, Jungwoo Lee

UMass Center for Clinical and Translational Science Research Retreat

Clinical stability occurs when cancers reach a state where the disease neither advances nor regresses. Tumors can remain in this state for multiple years before progressing to more aggressive phenotypes. The mechanisms for maintaining a stable state and the factors that contribute to tumor activation are poorly understood. We hypothesized that an implantable biomaterial scaffold would be able to isolate a population of stable tumor cells that could then be used to study the transition to an aggressive phenotype. In this work we developed a tunable and highly controlled, porous acrylamide scaffold and subcutaneously implanted them in immunodeficient (NSG) mice ...


Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai 2016 University of Massachusetts Lowell

Transferrin Conjugated Polymeric Nanomedicine For Targeting Pancreatic Cancer Using Paclitaxel And Gemcitabine, Aniket Gad, Michael Tilton, Brandon Piel, Prakash Rai

UMass Center for Clinical and Translational Science Research Retreat

Pancreatic cancer (PanCa) has a dismal prognosis with five-year survival rates under 5%. PanCa is usally diagnosed at very late stages and even if diagnosed early, surgery is rarely an option. These factors contribute towards the bleak statistics for PanCa Chemo and radiation treatments having deleterious side-effects. There is therefore a clinical, unmet need for novel, targeted treatments with low morbidity in PanCa. Gemzar® (gemcitabine-HCl) is an FDA (Food and Drug Administration) approved chemotherapeutic drug that has been used to treat PanCa. However, intrinsic and acquired chemoresistance to gemcitabine contribute to the poor prognosis of PanCa. A combination of Abraxane ...


Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang 2016 University of Massachusetts Boston

Structural Activity Relationship Study On Dual Plk1 /Brd4 Inhibitor, Bi- 2536, Hailemichael Yosief, Shuai Liu, Dennis L. Buckley, Justin M. Roberts, Alex M. Muthengi, Francesca M. Corsini, James E. Bradner, Wei Zhang

UMass Center for Clinical and Translational Science Research Retreat

Polo-like kinase 1 (PLK1) and BRD4 are two different therapeutic targets in cancer drug discovery. Recently it has been reported that PLK1 inhibitor, BI-2536, is also a potent inhibitor of BRD4. The simultaneous inhibition of PLK1 and BRD4 by a single drug molecule is interesting because this could lead to the development of effective therapeutic strategy for different types of disease conditions in which PLK1 and BRD4 are implicated. Structural activity relationship studies has been carried out on BI-2536 to generate analogs with enhanced dual inhibitory activity against BRD4 and PLK1 as well as to render the molecule selective to ...


Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang 2016 University of Massachusetts Medical School

Identification Of Gdf-6 Blocking Antibodies As Anti-Melanoma Therapeutics, Ejemel Monir, Danielle Wisheart, Alec Gramann, Arvind Venkatesan, Mark S. Klempner, Craig J. Ceol, Yang Wang

UMass Center for Clinical and Translational Science Research Retreat

Through comparative oncogenomic studies and functional analyses, we have identified the bone morphogenetic protein (BMP) factor GDF6 as a new melanoma oncogene. The secreted, carboxy-terminal portion of GDF6 is the active form that binds to cell-surface receptors to initiate BMP signaling. Targeted antibodies directed against secreted proteins are a proven therapeutic modality in several diseases.

To develop therapeutic antibodies against the active form of GDF6, we generated a panel of monoclonal antibodies. Due to the high similarity of human and mouse GDF6 proteins, the C-terminal GDF6 protein was expressed as bacterial recombinant protein with fusion tags to enhance immunogenicity. The ...


Erbb2 Signaling Increases Androgen Receptor Expression In Abiraterone-Resistant Prostate Cancer, Shuai Gao, Huihui Ye, Sean Gerrin, Hongyun Wang, Ankur Sharma, Sen Chen, Akash Patnaik, Adam Sowalsky, Olga Voznesensky, Wanting Han, Ziyang Yu, Elahe Mostaghel, Peter S. Nelson, Mary-Ellen Taplin, Steven P. Balk, Changmeng Cai 2016 University of Massachusetts Boston

Erbb2 Signaling Increases Androgen Receptor Expression In Abiraterone-Resistant Prostate Cancer, Shuai Gao, Huihui Ye, Sean Gerrin, Hongyun Wang, Ankur Sharma, Sen Chen, Akash Patnaik, Adam Sowalsky, Olga Voznesensky, Wanting Han, Ziyang Yu, Elahe Mostaghel, Peter S. Nelson, Mary-Ellen Taplin, Steven P. Balk, Changmeng Cai

UMass Center for Clinical and Translational Science Research Retreat

Purpose: ErbB2 signaling appears to be increased and may enhance AR activity in a subset of CRPC, but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer (PCa), and determine whether it may contribute to androgen receptor (AR) signaling in these tumors.

Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone, and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover ...


Developing Anti-Gdf6 Therapeutics For Treatment Of Advanced Melanoma, Alec Gramann, Arvind Venkatesan, Ejemel Monir, Danielle Wisheart, Yan Wang, Craig J. Ceol 2016 University of Massachusetts Medical School

Developing Anti-Gdf6 Therapeutics For Treatment Of Advanced Melanoma, Alec Gramann, Arvind Venkatesan, Ejemel Monir, Danielle Wisheart, Yan Wang, Craig J. Ceol

UMass Center for Clinical and Translational Science Research Retreat

Melanoma, the leading cause of skin cancer death in the U.S., is increasing in incidence. Targeted therapies have been approved for treatment of advanced melanoma, but few patients experience extended survival benefit. In order to combat poor outcomes, new therapeutic targets are needed. Using cross-species oncogenomic analyses, our lab has identified a novel melanoma driver, Growth differentiation factor 6 (GDF6), a secreted bone morphogenetic protein (BMP) ligand that is amplified and overexpressed in human melanomas. Functional analyses show GDF6 acts via the BMP-SMAD1 pathway as a pro-survival factor in melanomas. Inhibiting GDF6 or the BMP pathway using shRNAs or ...


The Therapeutic Effects Of Per Os Artemisinin Delivered As Dried Leaf Artemisia Annuavs. Artesunate In Non-Small Cell Lung Cancer, Dina Rassias, Pamela Weathers 2016 Worcester Polytechnic Institute

The Therapeutic Effects Of Per Os Artemisinin Delivered As Dried Leaf Artemisia Annuavs. Artesunate In Non-Small Cell Lung Cancer, Dina Rassias, Pamela Weathers

UMass Center for Clinical and Translational Science Research Retreat

Artemisinin, the active component of Artemisia annua L. used to treat malaria, also has therapeutic efficacy against many types of cancer. Solubility issues led to development of more soluble semi-synthetic derivatives. Artesunate (ART), in particular, is a more soluble derivative of artemisinin and has profound cytotoxicity toward many types of tumor cells, but healthy cells are less sensitive. Artemisinin delivered per os as dried leaves, referred to as dried leaf artemisinin (DLA), was shown in rodent studies to improve bioavailability by more than 40-fold. ART has been widely studied for its anti-cancer properties, but it has yet to be shown ...


Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr. 2016 Clark Atlanta University

Id4 Acts As A Tumor Suppressor Via P53: Mechanistic Insight, Derrick J. Morton Jr.

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

Overexpression of tumor-derived mutant p53 is a common event in tumorigenesis, suggesting an advantageous selective pressure in cancer initiation and progression. Given that p53 is found to be mutated in 50% of all human cancers, restoration of mutant p53 to its wild type biological function has been a widely sought after avenue for cancer therapy. Most research efforts have largely focused on restoration of mutant p53 by artificial means given that p53 has some degree of conformational flexibility allowing for introduction of short peptides and artificial compounds. Recently, theoretical modeling and studies focused on restoration of mutant p53 by physiological ...


Epas1 Promotes Endothelial Cell Migration In An Irx3-Dependent Manner, Petrina K. Barnett 2016 Clark Atlanta University

Epas1 Promotes Endothelial Cell Migration In An Irx3-Dependent Manner, Petrina K. Barnett

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

Iroquois homeobox gene 3 (Irx3) is a transcription factor belonging to the Iroquois family of homeobox genes that is expressed in the embryonic organs of multiple organisms. Although much is known about Irx3 during embryogenesis, the cross talk of expression and function of Irx3 in peripheral vascular disease (PVD) remains to be investigated. Herein, we demonstrate that Endothelial PAS Domain 1 (EPAS1), which is involved in vasculogenesis and diseases associated with hypoxia, is an upstream regulator of Irx3, and this interaction contributes to the cellular movement of human microvascular endothelial cells (HMVECs). Genetic EPAS1 loss-of-function (LOF) studies in HMVECs resulted ...


Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

UT GSBS Dissertations and Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to ...


Characterization Of Stem Cell Turnover In A Living Epithelial Bilayer, Elizabeth Sumner 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

Characterization Of Stem Cell Turnover In A Living Epithelial Bilayer, Elizabeth Sumner

UT GSBS Dissertations and Theses (Open Access)

Homeostatic maintenance of epithelia requires the renewal and replacement of old or dying cells while sustaining a functional barrier. Imbalance between cell production and elimination are hypothesized to underlie many pathological conditions. However, our knowledge of cell turnover within living tissues remains largely restricted to static images due to the limited ability to study epithelia in their native context. Here we report that clearance of damaged basal stem cells promotes compensatory proliferation of neighboring stem cells to maintain overall population numbers in a bilayered epithelium. Time-lapse imaging and electron microscopy experiments reveal that dying cells are rapidly cleared as nearby ...


Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton 2016 East Tennessee State Universtiy

Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton

Electronic Theses and Dissertations

Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER ...


Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones 2016 University of Louisville

Microrna-186 And Metastatic Prostate Cancer., Dominique Zilpha Jones

Electronic Theses and Dissertations

MicroRNA (miR) dysregulation alters cancer-associated gene expression, which contributes to cancer pathogenesis. For example, miR-186 over expression lead to enhanced proliferation and migration in pancreatic cancer cell models. However, the role of miR-186 in prostate cancer (PCa) remains controversial. Previously, miR-186-5p was up-regulated in PCa patient serum (stage III/IV) compared to controls. Furthermore, miR-186-5p was up-regulated in metastatic PCa (PC-3, MDA PCa 2b, LNCaP) relative to normal prostate epithelial cells (RWPE1). We hypothesized miR-186 inhibition will reduce aggressive PCa using metastatic cell models. To test this, we evaluated whether miR-186-5p inhibition would reduce aggressive PCa behavior and overexpression induce ...


Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely 2016 University of Louisville

Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Previous ...


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