Open Access. Powered by Scholars. Published by Universities.®

Cancer Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 27 of 27

Full-Text Articles in Cancer Biology

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

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 ...


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 May 2016

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 ...


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

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 ...


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 May 2016

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 May 2016

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 ...


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 May 2016

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 ...


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

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 ...


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

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 ...


Implantable Microenvironments To Capture Stable-To- Aggressive Tumor Transition, Ryan Carpenter, Jungwoo Lee May 2016

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 ...


Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter May 2014

Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter

UMass Center for Clinical and Translational Science Research Retreat

The objective of this study is to deliver anti-pPKCθ (T538) into T cells (hPBMCs) by using cell penetrating peptide mimics (CPPMs) to neutralize PKCθ activity both in vitro and in vivo, with the eventual goal of treating aplastic anemia (AA). AA is an immune-mediated bone marrow failure disease caused by T helper type 1 (Th1) autoimmune responses, which destroy blood cell progenitors. It was previously reported that protein kinase C theta (PKCθ), expressed specifically in T cells, plays an important role in T cell signaling by mediating Th1 differentiation. Mice treated with Rottlerin, a pharmacological inhibitor of PKCθ, are rescued ...


Gene Expression Profiles Identify Features Common To Lobular And Ductal Premalignant Breast Lesions, Amy L. Roberts, D. Joseph Jerry, Kelly J. Gauger, Sallie S. Schneider, Giovanna M. Crisi, Grace Makari-Judson, Ashraf Khan, Karl Simin May 2014

Gene Expression Profiles Identify Features Common To Lobular And Ductal Premalignant Breast Lesions, Amy L. Roberts, D. Joseph Jerry, Kelly J. Gauger, Sallie S. Schneider, Giovanna M. Crisi, Grace Makari-Judson, Ashraf Khan, Karl Simin

UMass Center for Clinical and Translational Science Research Retreat

Premalignant lesions have been identified in both the ductal and lobular units of the breast epithelium. These lesions have a 4-fold increase in risk of progression to invasive breast cancer, but 80% will remain indolent. This may be due, in part, to the uncertainty of diagnoses as inter-observer reproducibility is poor. When treated with prophylactic hormone therapies blocking the estrogen receptor, up to 40% of women still develop tumors. Therefore the challenge is to develop diagnostic tests that identify the subset of high-risk lesions and provide appropriate prophylactic therapies. We undertook genome-wide expression studies to define sets of genes that ...


A Novel Approach To Targeted Oncologic Therapy - Co-Culture Viability Of Polymer Prodrug Conjugation To Mesenchymal Stem Cells, Kaitlyn Wong, Nicholas Panzarino, Samantha Mcrae Page, Richard Arenas, Sallie S. Schneider, Todd S. Emrick May 2014

A Novel Approach To Targeted Oncologic Therapy - Co-Culture Viability Of Polymer Prodrug Conjugation To Mesenchymal Stem Cells, Kaitlyn Wong, Nicholas Panzarino, Samantha Mcrae Page, Richard Arenas, Sallie S. Schneider, Todd S. Emrick

UMass Center for Clinical and Translational Science Research Retreat

Background/Purpose: Conjugation of polymer prodrugs to tumor homing cells, such as Mesenchymal Stem Cells (MSCs), could provide a vehicle for actively targeted delivery of polymer prodrugs.

Methods: Human Bone Marrow MSCs were conjugated to either a doxorubicin polymer prodrug or free doxorubicin and were co-cultured with T-cells. Viability was assessed through the use of a Vi-cell counter. In Vivo Migration Analysis was performed NOD SCID mice implanted with subcutaneous MDA MB-231 breast cancer xenografts. Following tumor establishment, mice were injected via lateral tail vein injection with either saline or polymer loaded MSCs. Five days following stem cell injection, mice ...


Targeted Destruction Of Triple Negative Breast Cancer Using Nanoparticles, Adeyinka C. Adejumo, Chinedu Charles Ochin, Rahul Jadia, Fulya Ekiz Kanik May 2014

Targeted Destruction Of Triple Negative Breast Cancer Using Nanoparticles, Adeyinka C. Adejumo, Chinedu Charles Ochin, Rahul Jadia, Fulya Ekiz Kanik

UMass Center for Clinical and Translational Science Research Retreat

Photodynamic therapy (PDT) is a combination of light and photosensitizing drug in which a photosensitizer is injected intravenously and accumulates in the tissue. This tissue is then irradiated by light at an appropriate wavelength and the drug leads to cytotoxicity with a cascade of biochemical responses which affects and inactivates the cancer cells in the tumor tissue. In the cells, PDT generally induces mitochondrial damage and apoptosis which destroy the tissue and induce an antitumor activity upon illumination. Benzoporphyrin-derivative verteporfin (BPD) and curcumin are two photosensitizer drugs having the capability in use of PDT. The therapeutic potential of BPD and ...


Inhibition Of Colon Cancer By Polyphenols From Whole Cranberry, Catherine Neto, Anne Liberty, Sarah Frade, Anuradha Tata, Tracie Ferreira, Mingyue Song, Xian Wu, Hang Xiao May 2014

Inhibition Of Colon Cancer By Polyphenols From Whole Cranberry, Catherine Neto, Anne Liberty, Sarah Frade, Anuradha Tata, Tracie Ferreira, Mingyue Song, Xian Wu, Hang Xiao

UMass Center for Clinical and Translational Science Research Retreat

The ability of cranberry fruit extracts to inhibit colon carcinogenesis is under investigation using a combination of in vitro and in vivo methods. Compounds isolated from cranberry fruit (Vaccinium macrocarpon) including oligomeric polyphenols known as proanthocyanidins (PACs) decreased the proliferation of HCT116 and HT-29 colon cancer cells, induced apoptosis and reduced the formation of tumor colonies. Treatment of HCT116 colon cancer cells with cranberry polyphenols produced changes in expression of genes and proteins associated with the MAPK pathway, confirmed by microarray analysis, quantitative (Q)-PCR and Western blotting. Based on cranberry's effect in vitro, a feeding study was conducted ...


Establishment Of Rab-11 Induced Inflammatory Regulation As Therapeutic Targets In Colon Cancer Progression, Yingchao Nie, Alla Amcheslavsky, Qi Li, Shiyan Yu, Nan Gao, Zhong Jiang, Michele Markstein, Y. Tony Ip May 2014

Establishment Of Rab-11 Induced Inflammatory Regulation As Therapeutic Targets In Colon Cancer Progression, Yingchao Nie, Alla Amcheslavsky, Qi Li, Shiyan Yu, Nan Gao, Zhong Jiang, Michele Markstein, Y. Tony Ip

UMass Center for Clinical and Translational Science Research Retreat

Colon cancer is the third-deadliest cancer in the United States. Better understanding the cancer microenvironment/niches is crucial to the development of successful therapeutic targets. An RNAi screening using enterocyte specific driver was performed in Drosophila melanogaster intestine to search for niches regulating the intestine stem cell homeostasis. A small GTPase, Rab11 caused strong intestine stem cell (ISC) proliferation and tissue hyperplasia upon knockdown, due to increased production of inflammatory cytokines and growth factors. Increased inflammatory cytokines and proliferation were also observed in mouse Rab11a knockout (KO) intestine, indicating Rab11 regulatory role in the inflammation-induced hyperplasia is evolutionarily conserved and ...


Antineoplastic Effects Of Rhodiola Crenulata On B16f10 Melanomas, Maxine Dudek, Richard B. Arenas, Kaityln Wong, Carmen Mora, Lotfi M. Bassa, Sallie S. Schneider May 2014

Antineoplastic Effects Of Rhodiola Crenulata On B16f10 Melanomas, Maxine Dudek, Richard B. Arenas, Kaityln Wong, Carmen Mora, Lotfi M. Bassa, Sallie S. Schneider

UMass Center for Clinical and Translational Science Research Retreat

Hypothesis: Rhodiola crenulata extract is derived from Tibetan plant’s roots and has been shown to have anti-cancer properties. Previously, we have shown that Rhodiola extract has toxic effects on B16 F10 mouse melanoma cells in vitro. The purpose of this project was to determine if a daily topical application of Rhodiola extract on melanoma tumors in mice leads to a reduction in tumor size and improved survival.

Methods: 1x106 B16F10 melanoma cells were subcutaneously injected above the scapular fat pad in C57/BL6 mice. Rhodiola extract was dissolved in a 10% DMSO Eucerine based cream. Twenty-four hours following tumor ...


Inhibition Of Bromodomain Proteins In Treatment Of Diffuse Large B-Cell Lymphoma, Sally E. Trabucco, Rachel M. Gerstein, Andrew M. Evens, James E. Bradner, Leonard D. Shultz, Dale L. Greiner May 2014

Inhibition Of Bromodomain Proteins In Treatment Of Diffuse Large B-Cell Lymphoma, Sally E. Trabucco, Rachel M. Gerstein, Andrew M. Evens, James E. Bradner, Leonard D. Shultz, Dale L. Greiner

UMass Center for Clinical and Translational Science Research Retreat

Only ~50% of patients with diffuse large B-cell lymphoma (DLBCL), the most common and aggressive subtype of non-Hodgkin’s lymphoma, enter long-term remission after standard chemotherapy, and patients who do not respond to treatment have few options. Therefore, there is a critical need for effective and targeted therapeutics for DLBCL. Recent studies highlight the incidence of increased c-MYC protein in DLBCL and the correlation between high levels of c-MYC and poor survival prognosis of DLBCL patients, suggesting that c-MYC is a compelling therapeutic target for DLBCL therapy. The small molecule JQ1 suppresses c-MYC expression through inhibition of the BET family ...


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.


A Case Of Mistaken Identity: Biomarkers For High Risk Premalignant Breast Lesions, D. Joseph Jerry, Karl Simin May 2013

A Case Of Mistaken Identity: Biomarkers For High Risk Premalignant Breast Lesions, D. Joseph Jerry, Karl Simin

UMass Center for Clinical and Translational Science Research Retreat

Discusses projects to develop biomarkers to predict atypical hyperplasias that may progress to invasive breast cancer. This presentation is part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.


Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio May 2013

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

UMass Center for Clinical and Translational Science Research Retreat

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.


Development Of Fluorescent Probes For Cancer Cell Lines, Zijuan Zhang, Nicholas Kwiatkowski, Hong Zeng, Sang Min Lim, Nathanael S. Gray, Priscilla Yang, Wei Zhang May 2013

Development Of Fluorescent Probes For Cancer Cell Lines, Zijuan Zhang, Nicholas Kwiatkowski, Hong Zeng, Sang Min Lim, Nathanael S. Gray, Priscilla Yang, Wei Zhang

UMass Center for Clinical and Translational Science Research Retreat

Fluorescence imaging is a powerful tool that permits visualization of specific cell states within a population; however, existing methods for fluorescence labeling cannot be easily applied in many biological systems. Unlike antibodies, small molecule proteins can be cell permeable and therefore useful in live-cell and in vivo imaging experiments; moreover, small molecule probes do not require genetic manipulation of cells.

Protein kinases are in many ways ideal targets for the development of selective fluorescent small molecule probes. This is because protein kinases are involved in most cellular processes and changes in their localization, accessibility, and abundance are associated with changes ...


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 ...


Global Prevention Of Adult Cancers, Vic Raso May 2013

Global Prevention Of Adult Cancers, Vic Raso

UMass Center for Clinical and Translational Science Research Retreat

Growth hormone receptor deficient (GHRD) individuals in Ecuador are cancer free their entire lifetime due to low insulin-like growth factor (IGF) levels. This IGF deficiency protected that small GHRD population from the wide array of 20 different cancer types that caused death in their IGF-replete relatives. This suggests that the initiation or progression of many human cancers is dependent on IGF.

Those GHRD individuals are short statured due to their life-long IGF deficit but otherwise are surprisingly healthy and long-lived (some >80 years old). Therefore, we are developing IGF-suppressive vaccines for use in fully grown adults with the hope of ...


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 ...


Pregnancy Induces Persistent Changes That Potentiate Apoptotic Signaling And Responses To Dna Damage, Mary J. Hagen, Amy L. Roberts, Karen A. Dunphy, Jeffrey L. Blanchard, Melissa A. Troester, Sallie S. Schneider, D. Joseph Jerry May 2013

Pregnancy Induces Persistent Changes That Potentiate Apoptotic Signaling And Responses To Dna Damage, Mary J. Hagen, Amy L. Roberts, Karen A. Dunphy, Jeffrey L. Blanchard, Melissa A. Troester, Sallie S. Schneider, D. Joseph Jerry

UMass Center for Clinical and Translational Science Research Retreat

A full-term pregnancy reduces the lifetime risk of breast cancer by up to 50%. This effect is mediated, in part, by p53-dependent pathways. Gene expression profiling was used to investigate the mechanisms that alter apoptotic responses to DNA damage in the mammary gland. Radiation-induced responses in BALB/c-Trp53+/+ and BALB/c-Trp53-/- mice identified 121 genes that were altered by radiation and p53 status (p53-IR). To determine the effect of parity, mice were mated, force-weaned and mammary glands were allowed to involute for 21 days (parous) and compared with age-matched nulliparous mice. Gene expression profiles were determined in mammary tissues from ...


Estrogen Receptor Beta Selectively Restricts Proliferation And Favors Surveillance In Mammary Epithelial Cells, Karen A. Dunphy, Erick Roman-Perez, Rehaneh Hooshyar, Mary J. Hagen, Amy L. Roberts, Mara Isel Guerrero-Zayas, D. Joseph Jerry May 2013

Estrogen Receptor Beta Selectively Restricts Proliferation And Favors Surveillance In Mammary Epithelial Cells, Karen A. Dunphy, Erick Roman-Perez, Rehaneh Hooshyar, Mary J. Hagen, Amy L. Roberts, Mara Isel Guerrero-Zayas, D. Joseph Jerry

UMass Center for Clinical and Translational Science Research Retreat

Estrogen (17β-estradiol) has paradoxical effects in both promoting and preventing breast cancer as estrogen activates proliferation, but also promotes p53-mediated surveillance pathways. Estrogen mediates its effects in target tissues through the activation of estrogen receptor subtypes: ERα and ERβ. To examine the capability of these receptors in mediating surveillance as opposed to proliferation, selective estrogen receptor agonists were compared with 17β-estradiol for induction of proliferation and radiation induced apoptosis in vivo. Transcriptional regulation of estrogen-responsive genes was also compared in mouse mammary epithelium in vivo and in the human mammary MCF7 cell line transduced with a repressible ERβ. Selective activation ...


Biosensing Using Particle-(Bio)Polymer Sensor Arrays, Vincent Rotello May 2011

Biosensing Using Particle-(Bio)Polymer Sensor Arrays, Vincent Rotello

UMass Center for Clinical and Translational Science Research Retreat

We have developed sensor arrays containing non-covalent gold nanoparticle-fluorescent polymer assemblies to identify and quantify biological targets in minutes using a platreader platform. These sensors can identify protein targets at nanomolar concentrations in both buffer and human serum, and to differentiate between species and even different strains of bacteria. In more recent studies we have demonstrated that these sensor systems can discriminate between isogenic healthy, cancerous and metastatic cells.