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Full-Text Articles in Medicine and Health Sciences

Igf-Ir Promotes Prostate Cancer Growth By Stabilizing Α5Β1 Integrin Protein Levels., Aejaz Sayeed, Carmine Fedele, Marco Trerotola, Kirat K Ganguly, Lucia R Languino Oct 2013

Igf-Ir Promotes Prostate Cancer Growth By Stabilizing Α5Β1 Integrin Protein Levels., Aejaz Sayeed, Carmine Fedele, Marco Trerotola, Kirat K Ganguly, Lucia R Languino

Department of Cancer Biology Faculty Papers

Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR) mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa) cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR …


Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell Sep 2013

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …


Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks Aug 2013

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …


Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo Aug 2013

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …


Cancer Metabolism: New Validated Targets For Drug Discovery., Federica Sotgia, Ubaldo E. Martinez-Outshoorn, Md, Michael P. Lisanti Aug 2013

Cancer Metabolism: New Validated Targets For Drug Discovery., Federica Sotgia, Ubaldo E. Martinez-Outshoorn, Md, Michael P. Lisanti

Kimmel Cancer Center Faculty Papers

Recent studies in cancer metabolism directly implicate catabolic fibroblasts as a new rich source of i) energy and ii) biomass, for the growth and survival of anabolic cancer cells. Conversely, anabolic cancer cells upregulate oxidative mitochondrial metabolism, to take advantage of the abundant fibroblast fuel supply. This simple model of "metabolic-symbiosis" has now been independently validated in several different types of human cancers, including breast, ovarian, and prostate tumors. Biomarkers of metabolic-symbiosis are excellent predictors of tumor recurrence, metastasis, and drug resistance, as well as poor patient survival. New pre-clinical models of metabolic-symbiosis have been generated and they genetically validate …


Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina Jul 2013

Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina

Kimmel Cancer Center Faculty Papers

No abstract provided.


Breast Cancer Antiestrogen Resistance 3 (Bcar3) Promotes Cell Motility By Regulating Actin Cytoskeletal And Adhesion Remodeling In Invasive Breast Cancer Cells., Ashley L Wilson, Randy S Schrecengost, Michael S Guerrero, Keena S Thomas, Amy H Bouton Jun 2013

Breast Cancer Antiestrogen Resistance 3 (Bcar3) Promotes Cell Motility By Regulating Actin Cytoskeletal And Adhesion Remodeling In Invasive Breast Cancer Cells., Ashley L Wilson, Randy S Schrecengost, Michael S Guerrero, Keena S Thomas, Amy H Bouton

Department of Cancer Biology Faculty Papers

Metastatic breast cancer is incurable. In order to improve patient survival, it is critical to develop a better understanding of the molecular mechanisms that regulate metastasis and the underlying process of cell motility. Here, we focus on the role of the adaptor molecule Breast Cancer Antiestrogen Resistance 3 (BCAR3) in cellular processes that contribute to cell motility, including protrusion, adhesion remodeling, and contractility. Previous work from our group showed that elevated BCAR3 protein levels enhance cell migration, while depletion of BCAR3 reduces the migratory and invasive capacities of breast cancer cells. In the current study, we show that BCAR3 is …


Bortezomib (Ps-341) Treatment Decreases Inflammation And Partially Rescues The Expression Of The Dystrophin-Glycoprotein Complex In Grmd Dogs., Karla P C Araujo, Gloria Bonuccelli, Caio N Duarte, Thais P Gaiad, Dayson F Moreira, David Feder, José E Belizario, Maria A Miglino, Michael P Lisanti, Carlos E Ambrosio Apr 2013

Bortezomib (Ps-341) Treatment Decreases Inflammation And Partially Rescues The Expression Of The Dystrophin-Glycoprotein Complex In Grmd Dogs., Karla P C Araujo, Gloria Bonuccelli, Caio N Duarte, Thais P Gaiad, Dayson F Moreira, David Feder, José E Belizario, Maria A Miglino, Michael P Lisanti, Carlos E Ambrosio

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity …


Roles And Mechanism Of Mir-199a And Mir-125b In Tumor Angiogenesis., Jun He, Yi Jing, Wei Li, Xu Qian, Qing Xu, Feng-Shan Li, Ling-Zhi Liu, Bing-Hua Jiang, Yue Jiang Feb 2013

Roles And Mechanism Of Mir-199a And Mir-125b In Tumor Angiogenesis., Jun He, Yi Jing, Wei Li, Xu Qian, Qing Xu, Feng-Shan Li, Ling-Zhi Liu, Bing-Hua Jiang, Yue Jiang

Computational Medicine Center Faculty Papers

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and …


Early Results Of Prostate Cancer Radiation Therapy: An Analysis With Emphasis On Research Strategies To Improve Treatment Delivery And Outcomes., Kosj Yamoah, Kwamena Beecham, Sarah E Hegarty, Terry Hyslop, Timothy Showalter, Joel Yarney Jan 2013

Early Results Of Prostate Cancer Radiation Therapy: An Analysis With Emphasis On Research Strategies To Improve Treatment Delivery And Outcomes., Kosj Yamoah, Kwamena Beecham, Sarah E Hegarty, Terry Hyslop, Timothy Showalter, Joel Yarney

Department of Radiation Oncology Faculty Papers

ABSTRACT: BACKGROUND: There is scant data regarding disease presentation and treatment response among black men living in Africa. In this study we evaluate disease presentation and early clinical outcomes among Ghanaian men with prostate cancer treated with external beam radiotherapy (EBRT). METHODS: A total of 379 men with prostate cancer were referred to the National Center for Radiotherapy, Ghana from 2003 to 2009. Data were collected regarding patient-and tumor-related factors such as age, prostate specific antigen (PSA), Gleason score (GS), clinical stage (T), and use of androgen deprivation therapy (ADT). For patients who received EBRT, freedom from biochemical failure (FFbF) …


Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky Jan 2013

Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky

Kimmel Cancer Center Faculty Papers

Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 …