Medical Specialties Commons^™

Choroidal Metastasis From Leiomyosarcoma In Two Cases, Eric Feinstein, Swathi Kaliki, Carol L Shields, Hormoz Ehya, Jerry A Shields

Wills Eye Hospital Papers

Leiomyosarcoma is a malignant tumor of mesenchymal cells and is the most common soft-tissue sarcoma. Leiomyosarcoma is a notably rare tumor in the ophthalmic region and can be of primary, secondary or metastatic origin. To the best of our knowledge, there has only been one published case of leiomyosarcoma metastasis to the choroid. In this case study, we report two cases of primary leiomyosarcoma with metastasis to the choroid of the eye. Both cases displayed systemic metastasis and showed response to high dose plaque radiotherapy. Despite its prevalence as the leading form of sarcoma, leiomyosarcoma rarely metastasizes to the ocular …

Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd

Department of Cancer Biology Faculty Papers

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …

Nfkb Disrupts Tissue Polarity In 3d By Preventing Integration Of Microenvironmental Signals, Sabine Becker-Weimann, Gaofeng Xiong, Saori Furuta, Ju Han, Irene Kuhn, Uri-David Akavia, Dana Pe'er, Mina J. Bissell, Ren Xu

Markey Cancer Center Faculty Publications

The microenvironment of cells controls their phenotype, and thereby the architecture of the emerging multicellular structure or tissue. We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. However, the factors that prevent integration of signaling pathways that merge form and function are still largely unknown. We have identified nuclear factor kappa B (NFkB) as a transcriptional regulator that disrupts important microenvironmental cues necessary for tissue organization. We compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant …

The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis

Journal Articles: Obstetrics & Gynecology

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of …

Failure Patterns In Resected Pancreas Adenocarcinoma: Lack Of Predicted Benefit To Smad4 Expression., Jordan M. Winter, Laura H. Tang, David S. Klimstra, Weiguo Liu, Irena Linkov, Murray F. Brennan, Michael I. DʼAngelica, Ronald P. Dematteo, Yuman Fong, William R. Jarnagin, Eileen M. OʼReilly, Peter J. Allen

Department of Surgery Faculty Papers

OBJECTIVE: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).

BACKGROUND: SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.

METHODS: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 >months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes …

Ron Knockdown And Ron Monoclonal Antibody Imc-Ron8 Sensitize Pancreatic Cancer To Histone Deacetylase Inhibitors (Hdaci)., Yi Zou, Gillian M. Howell, Lisa E. Humphrey, J. Wang, Michael G. Brattain

Journal Articles: Eppley Institute

Recepteur d'origine nantais (Ron) is overexpressed in a panel of pancreatic cancer cells and tissue samples from pancreatic cancer patients. Ron can be activated by its ligand macrophage stimulating protein (MSP), thereby activating oncogenic signaling pathways. Crosstalk between Ron and EGFR, c-Met, or IGF-1R may provide a mechanism underlying drug resistance. Thus, targeting Ron may represent a novel therapeutic strategy. IMC-RON8 is the first Ron monoclonal antibody (mAb) entering clinical trial for targeting Ron overexpression. Our studies show IMC-RON8 downmodulated Ron expression in pancreatic cancer cells and significantly blocked MSP-stimulated Ron activation, downstream Akt and ERK phosphorylation, and survivin mRNA …

Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon

Center for Translational Medicine Faculty Papers

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Tgf-Beta Suppresses Vegfa-Mediated Angiogenesis In Colon Cancer Metastasis., Liying Geng, Anathbandhu Chaudhuri, G. Talmon, James L. Wisecarver, J. Wang

Journal Articles: Eppley Institute

The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered FET cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These cells readily formed xenograft tumors in athymic nude mice. Importantly, FETα cells retained their response to TGF-beta-mediated growth inhibition, and, like the parental FET cells, expression of a dominant negative TGF-beta type II receptor (DNRII) in FETα cells (FETα/DNRII) abrogated responsiveness to TGF-beta-induced growth inhibition and apoptosis under stress conditions in vitro and increased metastatic potential in an orthotopic model in vivo, which indicates metastasis suppressor activity of TGF-beta signaling …

Impact Of Cryoablation On Tumor Immunity, Jesse Veenstra

Wayne State University Dissertations

Background and Objectives: Percutaneous cryoablation is a minimally invasive procedure for tumor debulking, which has the potential to initiate or amplify tumor immunity through the release of tumor-associated antigens and endogenous danger signals. However, enhanced immunity is rarely observed in treated patients, suggesting the need for mechanistic analysis. The goal is to determine how cryoablation affects tumor specific immunity and if the response can be improved through exogenous TLR9 stimulation.

Methodology: We evaluated anti-Her2/neu immunity following cryoablation in wt BALB/c and tolerant NeuT mice inoculated with neu or Her2 expressing mammary tumors TUBO and D2F2/E2 respectively. Mice were treated with …

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

Gsk3Β Inhibition Blocks Melanoma Cell/Host Interactions By Downregulating N-Cadherin Expression And Decreasing Fak Phosphorylation., Jobin K John, Kim H T Paraiso, Vito W Rebecca, Liliana P Cantini, Ethan V Abel, Nicholas Pagano, Eric Meggers, Rahel Mathew, Clemens Krepler, Victoria Izumi, Bin Fang, John M Koomen, Jane L Messina, Meenhard Herlyn, Keiran S M Smalley

Department of Cancer Biology Faculty Papers

This study addresses the role of glycogen synthase kinase (GSK)-3β signaling in the tumorigenic behavior of melanoma. Immunohistochemical staining revealed GSK3β to be focally expressed in the invasive portions of 12 and 33% of primary and metastatic melanomas, respectively. GSK3 inhibitors and small interfering RNA (siRNA) knockdown of GSK3β were found to inhibit the motile behavior of melanoma cells in scratch wound, three-dimensional collagen-implanted spheroid, and modified Boyden chamber assays. Functionally, inhibition of GSK3β signaling was found to suppress N-cadherin expression at the messenger RNA and protein levels, and was associated with decreased expression of the transcription factor Slug. Pharmacological …

Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × …

Trop-2 Inhibits Prostate Cancer Cell Adhesion To Fibronectin Through The Β1 Integrin-Rack1 Axis., Marco Trerotola, Jing Li, Saverio Alberti, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Trop-2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). Trop-2 has been suggested to regulate cell-cell adhesion, given its high homology with the other member of the Trop family, Trop-1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and claudin-7. However, a role for Trop-2 in cell adhesion to the extracellular matrix has never been postulated. Here, we show for the first time that Trop-2 expression in PrCa cells correlates with their aggressiveness. Using either shRNA-mediated silencing of Trop-2 in cells that endogenously express it, or ectopic expression of Trop-2 in cells that …

Transforming Growth Factor-Β Suppresses Metastasis In A Subset Of Human Colon Carcinoma Cells., Neka A.K. Simms, Ashwani Rajput, Elizabeth A. Sharratt, Melanie Ongchin, Carol A. Teggart, J. Wang, Michael G. Brattain

Journal Articles: Eppley Institute

BACKGROUND: TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling.

METHODS: To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation …

Increase In Muscle Mitochondrial Biogenesis Does Not Prevent Muscle Loss But Increased Tumor Size In A Mouse Model Of Acute Cancer-Induced Cachexia., Xiao Wang, Alicia M Pickrell, Teresa A Zimmers, Carlos T Moraes

Kimmel Cancer Center Faculty Papers

Cancer-associated cachexia is a complex metabolic condition characterized by the progressive loss of body fat and deterioration of muscle mass. Although the cellular and molecular mechanisms of cachexia are incompletely understood, previous studies have suggested mitochondrial dysfunction in murine models of cancer cachexia. To better understand the metabolic shift in cancer-induced cachexia, we studied the effects of enhanced oxidative capacity on muscle wasting using transgenic mice over-expressing Peroxisome Proliferator-Activated Receptor gamma Co-activator-1α (PGC-1α) in skeletal muscle in a Lewis lung carcinoma-implanted model. Increased mitochondrial biogenesis was observed in the skeletal muscle of tumor-implanted mice. However, these increases did not prevent …

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …

Erk2 Phosphorylation Of Serine 77 Regulates Bmf Pro-Apoptotic Activity., Y Shao, A E Aplin

Department of Cancer Biology Faculty Papers

B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells …

A Novel Interaction Between 12-Lipoxygenase And Β4 Integrin Plays A Role In Cancer Progression, Sangeeta Joshi

Wayne State University Dissertations

No abstract provided.

Gene Expression Signatures Modulated By Epidermal Growth Factor Receptor Activation And Their Relationship To Cetuximab Resistance In Head And Neck Squamous Cell Carcinoma., Elana J Fertig, Qing Ren, Haixia Cheng, Hiromitsu Hatakeyama, Adam Dicker Md, Phd, Ulrich Rodeck, Michael Considine, Michael F Ochs, Christine H Chung

Department of Radiation Oncology Faculty Papers

BACKGROUND: Aberrant activation of signaling pathways downstream of epidermal growth factor receptor (EGFR) has been hypothesized to be one of the mechanisms of cetuximab (a monoclonal antibody against EGFR) resistance in head and neck squamous cell carcinoma (HNSCC). To infer relevant and specific pathway activation downstream of EGFR from gene expression in HNSCC, we generated gene expression signatures using immortalized keratinocytes (HaCaT) subjected to ligand stimulation and transfected with EGFR, RELA/p65, or HRASVal12D.

RESULTS: The gene expression patterns that distinguished the HaCaT variants and conditions were inferred using the Markov chain Monte Carlo (MCMC) matrix factorization algorithm Coordinated Gene Activity …

The Development And Implementation Of An Anthropomorphic Head Phantom For The Assessment Of Proton Therapy Treatment Procedures, Paige A. Summers

Dissertations and Theses (Open Access)

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within …

Oncogene-Induced Nrf2 Transcription Promotes Ros Detoxification And Tumorigenesis., Gina M. Denicola, Florian A. Karreth, Timothy J. Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, Kenneth H. Yu, Charles J. Yeo, Eric S. Calhoun, Francesca Scrimieri, Jordan M. Winter, Ralph H. Hruban, Christine Iacobuzio-Donahue, Scott E. Kern, Ian A Blair, David A. Tuveson

Department of Surgery Faculty Papers

Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer. Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe2l2) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2. Indeed, somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and increase the constitutive transcription of Nrf2 target genes were recently identified, indicating that enhanced ROS detoxification and additional Nrf2 functions may …

Inhibition Of Phosphorylated C-Met In Rhabdomyosarcoma Cell Lines By A Small Molecule Inhibitor Su11274., Jinxuan Hou, Jixin Dong, Lijun Sun, Liying Geng, J. Wang, Jialin C. Zheng, Yan Li, Julia A. Bridge, Steven H. Hinrichs, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.

METHODS: The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle …

Mitostatin Is Down-Regulated In Human Prostate Cancer And Suppresses The Invasive Phenotype Of Prostate Cancer Cells., Matteo Fassan, Domenico D'Arca, Juraj Letko, Andrea Vecchione, Marina P Gardiman, Peter Mccue, Bernadette Wildemore, Massimo Rugge, Dolores Shupp-Byrne, Leonard G Gomella, Andrea Morrione, Renato V Iozzo, Raffaele Baffa

Kimmel Cancer Center Faculty Papers

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in …

In Vitro Migration Of Cytotoxic T Lymphocyte Derived From A Colon Carcinoma Patient Is Dependent On Ccl2 And Ccr2., Klara Berencsi, Pyapalli Rani, Tianqian Zhang, Laura Gross, Michael Mastrangelo, Neal J Meropol, Dorothee Herlyn, Rajasekharan Somasundaram

Department of Medical Oncology Faculty Papers

BACKGROUND: Infiltration of colorectal carcinomas (CRC) with T-cells has been associated with good prognosis. There are some indications that chemokines could be involved in T-cell infiltration of tumors. Selective modulation of chemokine activity at the tumor site could attract immune cells resulting in tumor growth inhibition. In mouse tumor model systems, gene therapy with chemokines or administration of antibody (Ab)-chemokine fusion proteins have provided potent immune mediated tumor rejection which was mediated by infiltrating T cells at the tumor site. To develop such immunotherapeutic strategies for cancer patients, one must identify chemokines and their receptors involved in T-cell migration toward …

Regulation Of The Androgen Receptor By Set9-Mediated Methylation., Luke Gaughan, Jacqueline Stockley, Nan Wang, Stuart R C Mccracken, Achim Treumann, Kelly Armstrong, Fadhel Shaheen, Kate Watt, Iain J Mcewan, Chenguang Wang, Richard Pestell, Craig N Robson

Kimmel Cancer Center Faculty Papers

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain …

Vimentin Is A Novel Akt1 Target Mediating Motility And Invasion., Q-S Zhu, K Rosenblatt, K-L Huang, G Lahat, R Brobey, S Bolshakov, T Nguyen, Z Ding, R Belousov, K Bill, X Luo, A Lazar, Adam Dicker, Md, Phd, G B Mills, M-C Hung, D Lev

Department of Radiation Oncology Faculty Papers

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving …

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …

Histogram Analysis Of Adc In Brain Tumor Patients, Debrup Banerjee, Jihong Wang, Jiang Li, Norbert J. Pelc (Ed.), Ehsan Samei (Ed.), Robert M. Nishikawa (Ed.)

Electrical & Computer Engineering Faculty Publications

At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, …