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Biotech / Medical : Indications -- Cancer -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (276)	10/12/2002 6:59:38 PM
From: blue_chip	Respond to of 1840

Look what MD Anderson's up to. Nice of them to do research when a Company already holds the patent to the wild type and modified strain. Nice to see them join the list of researchers, U of Alabama, U of Minn & a few others now looking at the reovirus. MD Anderson's technology commercialization description has some errors however. It incorrectly assumes that the wild type has not been used in animal models intravenously. www2.mdanderson.org Development of a Novel Reoviral Oncolytic Therapy for Hematologic Malignancy Background Mutations in the RAS oncogene appear to be the primary derangement driving malignant growth in approximately 30% of all cancers. Acute myelogenous leukemias have mutated RAS in 25 to 44% of cases. One major focus of current cancer research is targeting RAS positive cells for destruction. Recently it has been realized that viruses of the genus reovirus will actively replicate and spread within tumors that are RAS positive. In healthy individuals, infection of reovirus is usually asymptomatic. The high efficacy in tumor lysis coupled with the low apparent toxicity to normal hosts offers the potential for a new avenue in the treatment of cancer. The American Cancer Society estimates there will be over 1 million new cases of cancer in the United States in 2002, with 60,000 of them attributed to various leukemias. Competitive Advantages Previous publications have demonstrated the antitumor effect of reovirus when the virus is given by the intratumoral route. Although the intratumoral route is useful for demonstrating the potential of the system in animal models, it would not be applicable to leukemia and it would not be broadly applicable in the setting of solid tumors where the location and accessibility of metastatic lesions may limit this approach. An MD Anderson scientist has developed a modification of reovirus that can be administered intravenously rather than intratumorally. Preclinical studies have clearly demonstrated increased retention of the virus (versus the unmodified virus) in the circulation, low toxicity of the virus, and the ability of the virus to lyse RAS positive tumor cells in vitro and in vivo. Additional work in SCID mice is in progress. Advantages of the modification include preserved infectivity, blocked antibody interference, and prolonged clearance. utm-notes-db2.mdacc.tmc.edu Jeffrey J. Tarrand, MD Research Interests: Antifungal agents, aspergillosis, reoviridae, leukemia Translational work is also being done to develop a clinically useful reovirus therapeutic agent. Reoviruses exit cells only through cell lysis, and they exhibit no latent state. They grow in ras-positive cells and thus may be able to inhibit a wide variety of tumors. Fortunately, all normal cells constitutively express a double-stranded RNA recognition protein that, through a kinase cascade, can rapidly shut down viral replication. Thus, the therapeutic index for this live viral therapy is potentially high. We are currently attempting to adapt the virus for testing in a leukemia model. bloodjournal.org Reovirus therapy of lymphoid malignancies Tommy Alain, Kensuke Hirasawa, Kelly J Pon, Sandra G Nishikawa, Stefan J Urbanski, Yvonna Auer, Joanne Luider, Anita Martin, Randal N Johnston, Anna Janowska-Wieczorek, Patrick W K Lee, and Anna E Kossakowska* Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Calgary Laboratory Services, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada Calgary Laboratory Services, Calgary, AB, Canada; Department of Pathology, University of Calgary, Calgary, AB, Canada Calgary Laboratory Services, Calgary, AB, Canada Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Medical Biochemistry, University of Calgary, Calgary, AB, Canada Department of Medicine, University of Alberta, Edmonton, AB, Canada Cancer Biology Research Group, University of Calgary, Calgary, AB, Canada; Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, AB, Canada * Corresponding author; email: anna.kossakowska@cls.ab.ca. Reoviruses infect cells that manifest an activated Ras-signaling pathway, and have been shown to effectively destroy many different types of neoplastic cells, including those derived from brain, breast, colon, ovaries, and prostate. In this study, we investigated reovirus as a potential therapeutic agent against lymphoid malignancies. A total of 9 lymphoid cell lines and 27 primary human lymphoid malignancies, as well as normal lymphocytes and hematopoietic stem/progenitor cells, were tested for susceptibility to reovirus infection. For in vitro studies, the cells were challenged with reovirus (serotype 3 Dearing), and viral infection was assessed by cytopathic effects, viability, viral protein synthesis and progeny virus production. We present evidence of efficient reovirus infection and cell lysis in the diffuse large B-cell lymphoma cell lines and Burkitt's lymphoma cell lines Raji and CA46 but not Daudi, Ramos and ST486. Moreover, when Raji and Daudi cell lines were grown subcutaneously in SCID/NOD mice and subsequently injected with reovirus intratumorally or intravenously, significant regression was observed in the Raji but not the Daudi induced tumors, which is consistent with the in vitro results. Susceptibility to reovirus infection was also detected in 21 of the 27 primary lymphoid neoplasias tested but not in the normal lymphocytes or hematopoietic stem/progenitor cells. Our results suggest that reovirus may be an effective agent against several types of human lymphoid malignancies.

To: scaram(o)uche who wrote (276)	10/14/2002 1:26:00 PM
From: scaram(o)uche	Respond to of 1840

one session for EORTC-NCI-AACR, haven't looked at it yet....... Thursday 21 November 2002 Poster session: New drug targets Poster Gleason-Guzman, Mary Telomestatin has a mixed type of binding modes with G-quadruplexes: intercalation between G-tetrads and end-stacking in the loop regions of intramolecular G-quadruplexes. Poster Werle-Schneider, Gisela Gene expression profiles in rat liver slices after treatment with different hepatic tumour promotors Poster Welsh, Sarah PX-478, a potent inhibitor of hypoxia-inducible factor-1 (HIF-1) and antitumor agent Poster Dai, Fangping G-quadruplex interaction of 3,6,9-trisubstituted acridines leads to specific telomerase inhibition, induction of senescence and telomere shortening Poster Coon, Mike Inhibition of lysophosphatidic acid acyltransferase-beta (LPAAT-b) by CT-32228 inhibits activation of RAS-RAF-Erk and PI3K/AKT/m-TOR pathways and selectively induces tumor cell apoptosis Poster Nitiss, John The unfolded protein response pathway plays a key role in anti-cancer drug sensitivity Poster Neumann, Beate Identification of a new drug target using RNAi-based functional genomics Poster Ostman, Arne PDGF receptor inhibition in tumor stroma, with STI571 or PDGF B-chain aptamers, enhances the effects of chemotherapy in experimental solid tumors by increasing tumor drug uptake Poster Malyukova, Alena Tumor suppressor genes in chromosome 3p21.31 Poster Mercola, D. The transcription factor Egr-1 promotes prostate carcinoma and systemic treatment of TRAMP mice with antisense Egr-1 inhibits tumour formation. Poster Trepicchio, William Molecular class prediction of acute myeloid leukemia and myelodysplastic syndromes Poster Clarke, Paul A. Gene expression microarray and 2D proteomic profiling of human ovarian adenocarcinoma cells following treatment with 17AAG, an inhibitor of the molecular chaperone Hsp90 Poster Lu, Y. Cloning of tumor metastasis associated cDNA fragments (est)in human lung giant cell carcinoma Poster Braga, Eleonora Hypermethylation of RASSF1A CpG promoter region and deletion aberrations in 3p21.31 LUCA region in major epithelial tumors Poster Hiroshi, M. Signal therapy of RAS cancers by blocking PAK pathways Poster Putzer, Brigitte M. Implications of N-terminal truncated p73 for Cancer Poster Lampidis, Theodore J. Hypoxia hypersensitizes the slow-growing cells of solid tumors to glycolytic inhibitors Poster Sakoff, Jennette A. Protein Phosphatase 2A, a novel and unexplored anticancer target Poster Weinstein, John N. An integrated approach to the pharmacogenomics and pharmacoproteomics of cancer Poster Kumar, Chandra Inhibition of Akt signaling in tumor cells leads to induction of apoptosis: studies using adenovirus-mediated delivery of an Akt dominant negative mutant Poster Powell, James The follicular thyroid carcinoma associated pax8/PPAR-gamma-1 fusion gene permits anchorage independent growth in a follicular thyroid cell line Poster Perrin, Steven A pharmacogenomics strategy for validation of cancer therapeutics using murine xenograph models Poster Gabrielli, Brian Tumor-selective toxicity of histone deacetylase inhibitors is due to their targeting cell cycle checkpoint points Poster Kroning, Relef Cellular accumulation of cisplatin is mediated by the ubiquitously expressed sodium-dependent human ASCT1-amino acid transporter. Poster Hofmann, J. New hydrazones, a novel class of experimental antitumor agents Poster de Vries, Peter CT-32228: a lysophosphatidic acid acyltransferase-beta (LPAAT-b) inhibitor, induces apoptosis in a variety of solid tumor, leukemia and lymphoma cell lines, but not in normal cells Poster Park, Jung-Hyun Diverse and unique cellular effects of SK-7068, a novel histone deacetylase inhibitor Poster Hagios, Carmen Linking genotype to phenotype: production and large scale functional analysis of gene knockouts in human cancer cells Poster Hays, John Differential kinetic properties of monomeric and oligomeric phosphorylated c-met. Poster Sambucetti, Lidia Correlation between NF-kB activity and IkB degradation in tumor cells using bioluminescent reporters Poster Janssen, Samuel Identification of tumor associated protease substrates using combinatorial chemistry Poster Majumder, S. Novel mammalian chromatin reconstitution in vivo Poster Turkson, James Novel peptidomimetic inhibitors of Stat3 signaling and oncogenesis Poster Langer, M. Insight into the mode of action of rViscumin through transcriptional profiling Poster Remiszewski, Stacy Preclinical efficacy, toxicology and pharmacokinetics of NVP-LAQ824, a novel synthetic histone deacetylase inhibitor Poster Verheij M. Lipid rafts as gateway for antitumor alkyl-lysophospholipids to induce apoptosis Poster Doroshow, James NADPH Oxidase 1 (NOX 1): A novel target for colon cancer therapy Poster Efferth, Thomas Molecular modes of action of antimalarial artemisinin derivatives as novel anticancer drugs Poster Bagnato, Anna Blockade of endothelin A receptor by ABT 627 suppresses tumor growth, neovascularization and potentiates cytotoxic paclitaxel activity in ovarian cancer cells in vitro and in vivo Poster Cox, Adrienne Ras and Rho GTPases: targets of FTase and GGTase I inhibitors for cancer treatment? Poster Wolf, Maija A strategy for identification of gene targets by integrating genome and transcriptome data in cancer Poster Glaser, Keith Characteristics of novel non-hydroxamate inhibitors of histone deacetylases Poster Carbone, David Lung cancer molecular fingerprinting: expression profiling of gene and protein with cDNA microarray and MALDI-TOF MS Poster Wachtel, Marco Paired-box containing transcription factors as targets for therapy in solid tumors, melanomas and brain tumors Poster Wood, Mike Approaches to structure-based drug discovery for the HSP-90 family Poster Marme, Alexander A protein containing the DHHC domain is upregulated in ovarian carcinomas. Poster Walter-Yohrling, Jennifer Gene expression profiling of tumor cells with varying levels of stromal involvement: a novel in vitro model for studying tumor-stroma interactions Poster Parker, Catriona Characterisation of CA-IX expression and activity in human tumour cell lines Poster Curwen, Jon O. ZD4054: a specific endothelin A receptor antagonist with potential utility in prostate cancer and metastatic bone disease Poster Harisi, R. Extracellular matrix of human osteosarcoma as a potential new therapeutic target Poster Hoffman Robert In vivo cellular and molecular multicolor imaging with GFP and RFP Poster Borden, Ernest Targeting of phosphatases (PTPases) by sodium stibogluconate (SSb) in WM-9 human melanoma for potentiation of Stat-1 phosphorylation and for antitumor effects Poster Gaiger, A. Identification of genes associated with multiple myeloma and monoclonal gammopathy of undetermined significance using the myeloma microarray Poster Atadja, Peter The histone deacetylase inhibitor LAQ824 is selectively toxic to tumor cell lines including multidrug resistant cells Poster Nakaigawa, Noboru Inactivation of VHL gene induces constitutive phosphorylation of MET protein in clear cell renal carcinoma : MET protein as a novel target for renal carcinoma therapy Poster Clarke, Michael Prospective identification and isolation of breast cancer tumor initiating cells Poster Jaffar, Mohammed Novel nitroimidazoyluracil prodrug derivatives as tumour-selective inhibitors of the angiogenic enzyme thymidine phosphorylase Poster Eisenbrand G. Expression of calmodulin-sensitive phosphodiesterase in rat tumour cell line and non-malignant astrocytes Poster Pardo, Luis Eag1 potassium channel as cancer therapy target Poster Priebe, W. Nuclear factor-kB activation. a new target for drug design? Poster Hanauske-Abel, Hartmut M. A novel target for antifolates: The dihydrofolate reductase domain of the G1/S transit controlling protein eIF-5A. Poster Priebe, W. Targeting Jak3 with small molecules to inhibit T-cell activity Poster Leuschner, Carola N-3 fatty acids improve treatment efficacy of Phor14-beta3 in nude mice with prostate cancer xenografts Poster Westwick, John Probing the role of JNK in transformed cell proliferation and survival Poster Warner, Steven Targeting a protein tyrosine phosphatase, PRL-1, for the treatment of pancreatic cancer. Poster Screpanti, I. Combined expression of pTa and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis Poster Grand, Cory Quadruplex formation in the c-MYC promoter inhibits protein binding and correlates with in vivo promoter activity Poster Pfahl, Magnus Additive/Synergistic interaction between MKP-1 inhibitors and anti-cancer drugs in human non-small-cell lung cancer cell H292. Poster Pfahl, Magnus New differentiation-involution inducing agents for the treatment of breast cancer. Poster Pfahl, Magnus Novel inhibitors of MKP-1 have potent anti-cancer activity in vivo. Poster Langer, M. alpha2-6-sialylated neolacto-series gangliosides serve as receptors for the anticancer drug rViscumin Poster Bigioni, Mario Effect of NK1 and NK2 tachykinin receptor antagonists on the growth of human breast carcinoma cell line, MDA-MB-231 Poster Hammond, L. Phase I and pharmacokinetic (PK) Trial of 3'-C-ethylnylcytidine (TAS-106) in solid tumors. Poster Crawford, Keith Novel ceramide analogues display selective cytotoxicity for drug-resistant breast tumor cells over normal breast epithelial cells Poster Menendez, J.A. The angiogenic factor CYR61, a downstream effector of heregulin, protects breast cancer cells from paclitaxel-induced cell death through integrin alphav beta3 Poster Mueerkoester, Susanne NFkappaB repression by sulfasalazine sensitizes pancreatic carcinoma cells to cytostatic drugs in vivo: a new concept of combined chemotherapy Poster Ferruzzi, Erendira Validation of reliable assay methods for glutathione quantitation and glutathione s-transferase activity in cancer patients Poster Wesierska-Gadek, Jozefa Activation of wt p53 protein in normal and tumor cells by a novel anti-cancer drug CHS 828 Poster Morosetti, Roberta PPARgamma ligands modulate PPARgamma and RARbeta expression in human glioblastoma cell lines. Poster Johnson, Steven Establishment of a chemotherapeutic drug/gene expression database for the molecular pharmacology of cancer. Poster Gasperi-Campani Anna Growth suppressive effect and apoptosis induction by N-(4-hydroxy phenyl) retinamide in human osteosarcoma cells in vitro Poster Grabowski, Patricia Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma Poster Frei, Eva Carbohydrate mimics bind to tumour cell surfaces and inhibit cell adhesion Poster Pecher, Stefana Endothelin a receptor blockade with atrasentan does not change PSA secretion in prostate cancer cell lines Poster Shi, Gongyi Image guided proteomics for molecular target discovery: a human giloma study Poster Coley, H. The cyclin-dependent kinase inhibitor cyc202 is effective in human leiomyosarcoma (LMS) cell lines in combination with doxorubicin Poster Gibson, Paul Cytochrome P450 1B1 (CYP1B1) is expressed in human colon adenocarcinomas, but its expression is not limited to the malignant epithelial cells. Poster Seaton, Angela Elucidation of the molecular mechanism underlying the anti-invasive activity of a novel proteasome inhibitor (Bz-Leu-Leu-Leu-COCHO)