drug synergism


Top Publications

  1. ncbi Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies
    Ting Chao Chou
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Pharmacol Rev 58:621-81. 2006
  2. ncbi Drug combination studies and their synergy quantification using the Chou-Talalay method
    Ting Chao Chou
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 70:440-6. 2010
  3. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
  4. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
  5. ncbi ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor
    Christin Tse
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Cancer Res 68:3421-8. 2008
  6. ncbi Drug synergism: its detection and applications
    R J Tallarida
    Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Pharmacol Exp Ther 298:865-72. 2001
  7. ncbi Synergy, antagonism, and what the chequerboard puts between them
    F C Odds
    J Antimicrob Chemother 52:1. 2003
  8. ncbi Synergy research: approaching a new generation of phytopharmaceuticals
    H Wagner
    Department of Pharmacy, Center of Pharma Research, Ludwig Maximilians University, Butenandtstr 5 13, House B, D 81377 Munich, Germany
    Phytomedicine 16:97-110. 2009
  9. ncbi The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas
    Peter Pyrko
    Department of Pathology, and University of Southern California Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
    Cancer Res 67:9809-16. 2007
  10. pmc Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
    Hal E Broxmeyer
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Exp Med 201:1307-18. 2005

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Publications305 found, 100 shown here

  1. ncbi Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies
    Ting Chao Chou
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Pharmacol Rev 58:621-81. 2006
  2. ncbi Drug combination studies and their synergy quantification using the Chou-Talalay method
    Ting Chao Chou
    Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 70:440-6. 2010
    ..This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively...
  3. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
    ..Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity...
  4. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
  5. ncbi ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor
    Christin Tse
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Cancer Res 68:3421-8. 2008
    ..The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens...
  6. ncbi Drug synergism: its detection and applications
    R J Tallarida
    Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Pharmacol Exp Ther 298:865-72. 2001
    ..Even when a single drug (or site) is used, its introduction places it in potential contact with a myriad of chemicals already in the system, a fact that underscores the importance of this topic in other areas of biological investigation...
  7. ncbi Synergy, antagonism, and what the chequerboard puts between them
    F C Odds
    J Antimicrob Chemother 52:1. 2003
  8. ncbi Synergy research: approaching a new generation of phytopharmaceuticals
    H Wagner
    Department of Pharmacy, Center of Pharma Research, Ludwig Maximilians University, Butenandtstr 5 13, House B, D 81377 Munich, Germany
    Phytomedicine 16:97-110. 2009
    ..This new generation of phytopharmaceuticals could lend phytotherapy a new legitimacy and enable their use to treat diseases which have hitherto been treated using synthetic drugs alone...
  9. ncbi The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas
    Peter Pyrko
    Department of Pathology, and University of Southern California Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
    Cancer Res 67:9809-16. 2007
  10. pmc Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
    Hal E Broxmeyer
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Exp Med 201:1307-18. 2005
    ..These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization...
  11. pmc Synergistic drug combinations tend to improve therapeutically relevant selectivity
    Joseph Lehar
    CombinatoRx Inc, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:659-66. 2009
    ..The context specificity of synergistic combinations creates many opportunities for therapeutically relevant selectivity and enables improved control of complex biological systems...
  12. ncbi Mechanisms of drug combinations: interaction and network perspectives
    Jia Jia
    Bioinformatics and Drug Design Group, Department of Pharmacy, Department of Biological Science, Center for Computational Science and Engineering, National University of Singapore, Singapore 117543
    Nat Rev Drug Discov 8:111-28. 2009
    ..Analysis of the 117 drug combinations identified reveals general and specific modes of action, and highlights the potential value of molecular interaction profiles in the discovery of novel multicomponent therapies...
  13. pmc Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib
    Nickolay Neznanov
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Oncotarget 2:209-21. 2011
    ..These results provide support for using combination treatments that disrupt the balance of PS and HSR to increase the therapeutic index of anticancer therapies...
  14. ncbi Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis
    Alok C Bharti
    Cytokine Research Section, Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Blood 101:1053-62. 2003
  15. pmc Drug interactions and the evolution of antibiotic resistance
    Pamela J Yeh
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Microbiol 7:460-6. 2009
    ..Furthermore, theoretical models and new experiments suggest that antagonistic interactions between antibiotics can counteract the evolution of drug resistance...
  16. ncbi Enhancing the apoptotic and therapeutic effects of HDAC inhibitors
    Ailsa J Frew
    Cancer Immunology Program, The Peter MacCallum Cancer Centre, Trescowthick Research Laboratories, East Melbourne, Victoria, Australia
    Cancer Lett 280:125-33. 2009
    ..In addition, we highlight the ability of HDACi to synergise with other anti-cancer agents to potently kill tumor cells and discuss the possible molecular processes that underpin the combination effect...
  17. ncbi Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies
    V Raja Solomon
    Tumor Biology Group, Northeastern Ontario Regional Cancer Program at the Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario, Canada P3E 5J1
    Eur J Pharmacol 625:220-33. 2009
    ..Taken together, it appears that the efficacy of conventional cancer therapies can be dramatically enhanced if used in combination with CQ and its analogs...
  18. ncbi Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells
    Issam Ben Sahra
    Faculte de Medecine, Universite de Nice Sophia Antipolis, Institut Signalisation et Pathologies, Institut National de la Sante et de la Recherche Medicale, U895, Nice, France
    Cancer Res 70:2465-75. 2010
    ..Our study reinforces the growing interest of metabolic perturbators in cancer therapy and highlights the potential use of the combination of metformin and 2DG as an anticancerous treatment...
  19. ncbi Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines
    Weiguang Wang
    Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom
    Int J Cancer 104:504-11. 2003
    ..As DS has extensive preclinical and clinical experience, translating its anticancer usage from in vitro study to clinical trials is relatively straightforward...
  20. ncbi 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo
    Gregory Maschek
    Department of Cell Biology and Anatomy, University of Miami, School of Medicine, Miami, Florida 33101, USA
    Cancer Res 64:31-4. 2004
    ..Overall, these results, combined with our in vitro data, provide a rationale for initiating clinical trials using glycolytic inhibitors in combination with chemotherapeutic agents to increase their therapeutic effectiveness...
  21. pmc Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms
    Priya Uppuluri
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Antimicrob Agents Chemother 52:1127-32. 2008
    ..This drug synergism is attributable to two effects: first, calcineurin inhibitors render fluconazole fungicidal rather than simply ..
  22. pmc Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer
    Michael Graham Espey
    Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Free Radic Biol Med 50:1610-9. 2011
    ..These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer...
  23. pmc TRAIL/Apo-2L: mechanisms and clinical applications in cancer
    R K Srivastava
    Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy Greenebaum Cancer Center, 20 North Pine Street, Baltimore, MD 21201, USA
    Neoplasia 3:535-46. 2001
    ..Nontagged Apo-2L/TRAIL does not cause hepatotoxicity in monkeys and chimpanzees and in normal human hepatocytes. Thus, nontagged Apo-2L/TRAIL appears to be a promising new candidate for use in the treatment of cancer...
  24. pmc Revisiting the isobole and related quantitative methods for assessing drug synergism
    Ronald J Tallarida
    Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Pharmacol Exp Ther 342:2-8. 2012
  25. pmc Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer
    Christine L Hann
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
    Cancer Res 68:2321-8. 2008
    ..Taken together, these data have specific implications for the clinical development of Bcl-2 inhibitors for SCLC and broader implications for the testing of novel anticancer strategies in relevant preclinical models...
  26. ncbi Modeling of tumor growth and anticancer effects of combination therapy
    Gilbert Koch
    Department of Mathematics and Statistics, University of Konstanz, Germany
    J Pharmacokinet Pharmacodyn 36:179-97. 2009
    ..The unique feature of the presented approach is the ability to characterize the nature of combined drug interaction as well as to quantify the intensity of such interactions by assessing the time course of combined drug effect...
  27. ncbi Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines
    Silvia La Monica
    Department of Experimental Medicine, University of Parma, Via Volturno 39, 43100 Parma, Italy
    Biochem Pharmacol 78:460-8. 2009
    ..These data suggest that treatment with everolimus and gefitinib might be of value in the treatment of selected NSCLC patients that exhibit high tumor proliferative activity...
  28. ncbi Synergy and other interactions in phytomedicines
    E M Williamson
    The School of Pharmacy, University of London, United Kingdom
    Phytomedicine 8:401-9. 2001
    ..Herbs discussed include Ginkgo biloba, Piper methysticum (Kava-Kava), Glycyrrhiza glabra, Hypericum perforatum, Valeriana officinalis, Cannabis sativa, Salix alba and others...
  29. ncbi Enhancing antibiotic activity: a strategy to control Acinetobacter infections
    Sasitorn Chusri
    Natural Products Research Center and Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, Thailand
    J Antimicrob Chemother 64:1203-11. 2009
    ..We describe the activity of ellagic and tannic acids as adjuvants that enhance the activity of aminocoumarin antibiotics against multidrug-resistant (MDR) Acinetobacter baumannii...
  30. ncbi Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART
    J Kulkosky
    Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Blood 98:3006-15. 2001
    ..This novel observation suggests the agent may be an excellent candidate to augment HAART by inducing expression of latent HIV-1 with the ultimate goal of eliminating persistent viral reservoirs in certain individuals infected with HIV-1...
  31. ncbi Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time
    Keun Ho Ryu
    Pharmacology Team, Life Science R and D Center, SK Chemicals, Korea
    Thromb Res 124:328-34. 2009
    ..With these studies, we suggest that combinative therapy of GB and cilostazol might offer enhanced anti-thrombotic efficacies without increasing side-effects...
  32. ncbi Synergism between natural products and antibiotics against infectious diseases
    Shanmugam Hemaiswarya
    Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036, India
    Phytomedicine 15:639-52. 2008
    ..The mode of action of combination differs significantly than that of the same drugs acting individually; hence isolating a single component may lose its importance thereby simplifying the task of pharma industries...
  33. ncbi Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of DR5
    Heesue Kim
    Institute for Medical Sciences and Department of Surgery, Ajou University School of Medicine, Suwon, South Korea 442 749
    Cancer Res 66:1740-50. 2006
  34. ncbi Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models
    Limin Hu
    Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143 0556, USA
    Cancer Res 62:1087-92. 2002
    ..Our data suggest that a combination of a PI3k inhibitor and conventional chemotherapy may provide an effective approach to inhibiting tumor growth and ascites production in ovarian cancer with acceptable side effects...
  35. ncbi The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma
    Philipp Baumann
    Department of Hematology and Oncology Medizinische Klinik Innenstadt, Klinikum der Universitat Munchen, Germany
    Exp Cell Res 315:485-97. 2009
    ..Taken together, inhibition of PI3 kinase/mTOR by NVP-BEZ235 is highly effective and NVP-BEZ235 represents a potential new candidate for targeted therapy in multiple myeloma...
  36. ncbi Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma
    Victor Y Yazbeck
    Department of Lymphoma Myeloma, The University of Texas M D Anderson Cancer Center, Houston, Tex 77030, USA
    Exp Hematol 36:443-50. 2008
    ..To investigate the mechanisms of antiproliferative effect induced by the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in mantle cell lymphoma (MCL)...
  37. ncbi Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products
    Ajaikumar B Kunnumakkara
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Res 67:3853-61. 2007
    ..018 versus control). Overall, our results suggest that curcumin potentiates the antitumor effects of gemcitabine in pancreatic cancer by suppressing proliferation, angiogenesis, NF-kappaB, and NF-kappaB-regulated gene products...
  38. pmc Heat shock protein 90 inhibitor is synergistic with JAK2 inhibitor and overcomes resistance to JAK2-TKI in human myeloproliferative neoplasm cells
    Warren Fiskus
    The University of Kansas Cancer Center, Kansas City, USA
    Clin Cancer Res 17:7347-58. 2011
    ..1.7 and UKE-1) or primary human CD34(+) myeloproliferative neoplasm (MPN) cells...
  39. ncbi Dual PI3K/AKT/mTOR inhibitor BEZ235 synergistically enhances the activity of JAK2 inhibitor against cultured and primary human myeloproliferative neoplasm cells
    Warren Fiskus
    The University of Kansas Cancer Center, Kansas City, KS, USA
    Mol Cancer Ther 12:577-88. 2013
    ..These findings create a compelling rationale to determine the in vivo activity of dual PI3K/mTOR inhibitors in combination with JAK inhibitors against myelofibrosis HPCs...
  40. ncbi Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia
    C Simioni
    Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy
    Leukemia 26:2336-42. 2012
    ..Taken together, our findings indicate that Akt inhibition may represent a potential therapeutic strategy in T-ALL...
  41. ncbi HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT
    Francesca Bruzzese
    Experimental Pharmacology Unit, Department of Research, National Cancer Institute Fondazione G Pascale, Naples, Italy
    J Cell Physiol 226:2378-90. 2011
    ..Overall, this study suggests that the vorinostat/gefitinib combination represents a promising therapeutic strategy that warrants further clinical evaluation in SCCHN, including tumors intrinsically resistant to EGFR-inhibitors...
  42. pmc Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma
    Saadia A Aziz
    Department of Pathology, Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06510, USA
    Clin Cancer Res 16:6029-39. 2010
    ..Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K...
  43. ncbi Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells
    X Yang
    The Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA
    Cancer Res 61:7025-9. 2001
    ..These data suggest that the activities of both DNMT1 and HDAC are key regulators of methylation-mediated ER gene silencing...
  44. ncbi Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors
    Elizabeth Buck
    Translational Research, Cancer Biology, OSI Pharmaceuticals, Farmingdale, New York 11735, USA
    Cancer Res 68:8322-32. 2008
    ..Collectively, these data show that resistance to inhibition of MEK, mTOR, and EGFR is associated with enhanced IGF-IR-directed Akt signaling, where all affect feedback loops converging at the level of IRS-1...
  45. ncbi Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors
    Kate F Whitecross
    Cancer Immunology Program, The Peter MacCallum Cancer Centre, Trescowthick Research Laboratories, East Melbourne, Australia
    Blood 113:1982-91. 2009
    ..Our studies provide important preclinical data on the binding specificity of ABT-737 and its usefulness against primary hematologic malignancies when used as a single agent and in combination with HDACi...
  46. ncbi Buthionine sulfoximine enhancement of arsenic trioxide-induced apoptosis in leukemia and lymphoma cells is mediated via activation of c-Jun NH2-terminal kinase and up-regulation of death receptors
    Duo Chen
    Division of Hematology Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029 6547, USA
    Cancer Res 66:11416-23. 2006
    ..These observations suggest that a DR-mediated pathway activated by JNK is involved in apoptosis induced by treatment with As(2)O(3) plus BSO...
  47. ncbi Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects
    Julien Verrax
    PMNT Unit, Louvain Drug Research Institute, Universite Catholique de Louvain, 1200 Bruxelles, Belgium
    Free Radic Biol Med 47:32-40. 2009
    ..Taken together, these results confirm that oral and parenteral administration of ascorbate are not comparable, the latter resulting in pharmacologic concentrations of ascorbate that exhibit interesting anticancer properties...
  48. ncbi Enhanced caspase-8 recruitment to and activation at the DISC is critical for sensitisation of human hepatocellular carcinoma cells to TRAIL-induced apoptosis by chemotherapeutic drugs
    T M Ganten
    Divison of Apoptosis Regulation, German Cancer Research Center DKFZ, Heidelberg, Germany
    Cell Death Differ 11:S86-96. 2004
  49. ncbi Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells
    Jie Li
    Department of General Surgical Science Surgery I, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371 8511, Japan
    Ann Surg Oncol 16:761-71. 2009
    ..However, 5-FU resistance in the course of treatment has become more common. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored...
  50. ncbi Small molecule XIAP inhibitors enhance TRAIL-induced apoptosis and antitumor activity in preclinical models of pancreatic carcinoma
    Meike Vogler
    University Children s Hospital, Ulm University, Ulm, Germany
    Cancer Res 69:2425-34. 2009
    ..These findings build the rationale for further (pre)clinical development of XIAP inhibitors and TRAIL against pancreatic cancer...
  51. ncbi (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78
    Svetlana P Ermakova
    Hormel Institute, University of Minnesota, Austin, Minnesota
    Cancer Res 66:9260-9. 2006
  52. pmc Sorafenib inhibits STAT3 activation to enhance TRAIL-mediated apoptosis in human pancreatic cancer cells
    Shengbing Huang
    Divisions of Oncology and Gastroenterology Hepatology, Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA
    Mol Cancer Ther 9:742-50. 2010
    ..These data indicate that targeting STAT3 may enhance treatment efficacy against pancreatic cancer...
  53. ncbi Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells
    Yiwei Li
    Department of Pathology and Internal Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Cancer Res 65:6934-42. 2005
    ..Theses results warrant carefully designed clinical studies investigating the combination of soy isoflavones and commonly used chemotherapeutic agents for the treatment of human cancers...
  54. ncbi Epigenetics and cancer treatment
    Lasse Sommer Kristensen
    Institute of Human Genetics, The Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark
    Eur J Pharmacol 625:131-42. 2009
    ..Finally, we will discuss the potential of DNA methylation changes as biomarkers to be used in diverse areas of cancer treatment, especially for predicting response to treatment with DNMT and HDAC inhibitors...
  55. ncbi Prospects for plant-derived antibacterials
    Kim Lewis
    Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA
    Nat Biotechnol 24:1504-7. 2006
    ..Can weakly active phytochemicals be combined synergistically to produce new antibacterial treatments?..
  56. ncbi Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates
    Song Li
    Department of Cancer Chemoprevention, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Mol Cancer Ther 6:1031-8. 2007
    ..The functional significance of Bim was confirmed by the observation that RNA interference of Bim markedly reduced the potency of selenium/doxorubicin to induce apoptosis...
  57. ncbi Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors
    Romina Marone
    Department of Biomedicine, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland
    Mol Cancer Res 7:601-13. 2009
    ..Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential in metastatic melanoma therapy...
  58. pmc The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo
    Cheng Xiong Xu
    Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia, United States of America
    PLoS ONE 6:e20899. 2011
    ..Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy...
  59. ncbi Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer
    Penelope D Ottewell
    Academic Unit of Clinical Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK
    J Natl Cancer Inst 100:1167-78. 2008
    ..We investigated the effects of clinically achievable doses of doxorubicin (Dox) and Zol, given alone, in sequence, and in combination, on the growth of established breast tumors in vivo...
  60. ncbi Antimalarial drug synergism and antagonism: mechanistic and clinical significance
    Angus Bell
    Department of Microbiology, Moyne Institute of Preventive Medicine, University of Dublin Trinity College, Dublin 2, Ireland
    FEMS Microbiol Lett 253:171-84. 2005
    ..This review discusses recent findings on antimalarial drug interactions and some pitfalls in their analysis and interpretation. The conclusions are likely to have relevance to other antimicrobial agents...
  61. pmc Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models
    Emmanuel Thomas
    Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Hepatology 53:32-41. 2011
    ..RNA interference studies excluded the activation of the Toll-like receptor and nuclear factor κB pathways in the action of ribavirin...
  62. ncbi Caspase-3 cleaves XIAP in a positive feedback loop to sensitize melanoma cells to TRAIL-induced apoptosis
    M Hörnle
    Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Baden Wurttemberg, Germany
    Oncogene 30:575-87. 2011
    ..The molecular mechanism discovered here appears to have broader implications, because cleavage of XIAP was also shown to accompany cisplatin-induced sensitization of melanoma cells to TRAIL...
  63. ncbi Using chemopreventive agents to enhance the efficacy of cancer therapy
    Fazlul H Sarkar
    Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 740 Hudson Webber Cancer Research Center, 110 East Warren, Detroit, MI 48201, USA
    Cancer Res 66:3347-50. 2006
    ..In this article, we summarize the findings of recent investigations of chemopreventive agents in combination with cancer treatment regimens...
  64. ncbi Bacterial efflux pump inhibitors from natural sources
    Michael Stavri
    Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London 29 39 Brunswick Square, London, UK
    J Antimicrob Chemother 59:1247-60. 2007
    ..The resistance-modifying activities of many new chemical classes of EPIs warrant further studies to assess their potential as leads for clinical development...
  65. ncbi Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor
    Christele Desbois-Mouthon
    UPMC Univ Paris 06, Paris, France
    Clin Cancer Res 15:5445-56. 2009
    ..Therefore, we investigated whether the specific targeting of the IGF type 1 receptor (IGF-1R) might represent a new therapeutic approach for this tumor...
  66. ncbi Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice
    Roni Haklai
    Department of Neurobiochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel
    Cancer Chemother Pharmacol 61:89-96. 2008
  67. ncbi Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy
    Jennifer S Carew
    The Institute for Drug Development, Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, 14960 Omicron Drive, San Antonio, TX 78245, USA
    Cancer Lett 269:7-17. 2008
    ..Here we summarize the different mechanisms of HDAC inhibitor-induced apoptosis and discuss their use in combination with other anticancer agents...
  68. pmc Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression
    Dario Barbone
    Lung Biology Center, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 7:e52753. 2012
    ..Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies...
  69. ncbi Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase
    Ben C L Chan
    Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
    J Ethnopharmacol 137:767-73. 2011
    ..The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms...
  70. ncbi Plant-based antimicrobial studies--methods and approaches to study the interaction between natural products
    Sandy van Vuuren
    Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa
    Planta Med 77:1168-82. 2011
    ..The scientific validation of efficacious antimicrobial combinations could lead to patentable entities making research in the field of phytosynergy not only academically rewarding but also commercially relevant...
  71. pmc The proteasome inhibitor bortezomib enhances ATRA-induced differentiation of neuroblastoma cells via the JNK mitogen-activated protein kinase pathway
    Peihua Luo
    College of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Zhejiang University, Hangzhou, China
    PLoS ONE 6:e27298. 2011
    ..These findings provide the rationale for the development of a new therapeutic strategy for NB based on the pharmacological combination of ATRA and bortezomib...
  72. ncbi Dichloroacetate shifts the metabolism from glycolysis to glucose oxidation and exhibits synergistic growth inhibition with cisplatin in HeLa cells
    Jing Xie
    Department of Pharmacology and Biostatistics, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China
    Int J Oncol 38:409-17. 2011
  73. ncbi Apigenin induces apoptosis via tumor necrosis factor receptor- and Bcl-2-mediated pathway and enhances susceptibility of head and neck squamous cell carcinoma to 5-fluorouracil and cisplatin
    Leong Perng Chan
    Institute of Clinical Medicine, Department of Otolaryngology Head and Neck Surgery, Kaohsiung Medical University Chung Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    Biochim Biophys Acta 1820:1081-91. 2012
    ..Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood...
  74. ncbi In vitro sequence-dependent synergism between paclitaxel and gefitinib in human lung cancer cell lines
    Hua Cheng
    Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People s Republic of China
    Cancer Chemother Pharmacol 67:637-46. 2011
    ..The aim of this study was to test whether paclitaxel followed by gefitinib is superior to other treatment schedules of NSCLC cell lines and to clarify the underlying mechanisms...
  75. ncbi Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis
    Federica Servida
    Fondazione Matarelli, Dipartimento di Farmacologia Chemioterapia e Tossicologia medica, Universita degli Studi di Milano, Via Vanvitelli 32, 20129, Milan, Italy
    Invest New Drugs 29:1264-75. 2011
  76. ncbi Drug development from natural products: exploiting synergistic effects
    Gudrun Ulrich-Merzenich
    Medical Policlinic of the Rheinische Friedrich Wilhelms University of Bonn, Wilhelmstr 35 37, D 53111 Bonn, Germany
    Indian J Exp Biol 48:208-19. 2010
  77. pmc Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and microRNA levels
    Leo Kretzner
    Department of Translational Research, Clinical and Molecular Pharmacology, City of Hope and Beckman Research Institute, Duarte, California, USA
    Cancer Res 71:3912-20. 2011
    ..Thus, the HDACi vorinostat leads to both transcriptional and posttranscriptional changes to create a proapoptotic milieu, sensitizing cells to mitosis-specific agents such as AKis...
  78. ncbi Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer
    C N Sreekanth
    Integrated Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India
    Oncogene 30:3139-52. 2011
    ..As curcumin could effectively downregulate all these survival signals induced by paclitaxel, we suggest it as a potent chemosensitizer to improve the therapeutic index of paclitaxel...
  79. pmc Gambogic acid enhances proteasome inhibitor-induced anticancer activity
    Hongbiao Huang
    Department of Pathophysiology, Guangzhou Medical College, Guangdong, People s Republic of China
    Cancer Lett 301:221-8. 2011
    ..Therefore, the findings presented in this study demonstrate that natural product gambogic acid is a valuable candidate to be used in combination with proteasome inhibitors, thus representing a compelling anticancer strategy...
  80. pmc Mechanism of synergy between epigallocatechin gallate and beta-lactams against methicillin-resistant Staphylococcus aureus
    W H Zhao
    Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan
    Antimicrob Agents Chemother 45:1737-42. 2001
    ..EGCg synergizes the activity of beta-lactams against MRSA owing to interference with the integrity of the cell wall through direct binding to peptidoglycan...
  81. pmc Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Pauley Heart Center, Richmond, VA 23298, USA
    Proc Natl Acad Sci U S A 107:18202-7. 2010
    ..In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit...
  82. pmc Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model
    Fábio T Watanabe
    Universidade de Sao Paulo, Laboratory of Medical Investigation, Department of Urology Lim55, Sao Paulo SP, Brazil
    Clinics (Sao Paulo) 66:2121-4. 2011
    ..Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer...
  83. pmc Simultaneous inhibition of glutathione- and thioredoxin-dependent metabolism is necessary to potentiate 17AAG-induced cancer cell killing via oxidative stress
    Peter M Scarbrough
    Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52240, USA
    Free Radic Biol Med 52:436-43. 2012
    ..These results suggest that simultaneous targeting of both GSH and Trx metabolism could represent an effective strategy for chemosensitization in human cancer cells...
  84. ncbi Enhanced antitumor efficacy by the combination of emodin and gemcitabine against human pancreatic cancer cells via downregulation of the expression of XIAP in vitro and in vivo
    Zhao Hong Wang
    Department of Hepatobiliary Pancreatic Surgery, the Second Affiliated Hospital of Wenzhou Medical College, No 109, West Xue yuan Road, Wenzhou 325027, P R China
    Int J Oncol 39:1123-31. 2011
    ..This study suggests that emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in vitro and in vivo, which may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP...
  85. ncbi Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1
    Chong Zhang
    1Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
    Mol Cancer Ther 10:1264-75. 2011
  86. pmc Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs
    Anja Frömberg
    Institute of Pharmacology, Faculty of Medicine, Philipps University Marburg, Karl von Frisch Strasse 1, 35032 Marburg, Germany
    Cancer Chemother Pharmacol 67:1157-66. 2011
  87. ncbi Bortezomib targets the caspase-like proteasome activity in cervical cancer cells, triggering apoptosis that can be enhanced by nelfinavir
    A Bruning
    Department of Obstetrics and Gynecology, Campus Innenstadt, Ludwig Maximilians University Munich, Munich, Germany
    Curr Cancer Drug Targets 11:799-809. 2011
    ..These results suggest that both bortezomib and nelfinavir are effective agents against chemoresistant cervical cancer cells and might be of interest for clinical studies on cervical cancer patients with recurrent or metastatic cancer...
  88. pmc Synergistic antimicrobial activity between pentacyclic triterpenoids and antibiotics against Staphylococcus aureus strains
    Pooi Yin Chung
    School of Medicine and Health Sciences, Monash University, Sunway Campus, Malaysia
    Ann Clin Microbiol Antimicrob 10:25. 2011
    ..The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin) against reference strains of Staphylococcus aureus...
  89. ncbi MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth
    Yu wen Zhang
    Van Andel Research Institute, Grand Rapids, MI, USA
    Cancer Res 70:6880-90. 2010
    ..Our findings also indicate that simultaneously targeting the MET and EGFR pathways can provide synergistic inhibitory effects for the treatment of cancers in which both pathways are activated...
  90. ncbi Valproic acid in the complex therapy of malignant tumors
    J Hrebackova
    Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
    Curr Drug Targets 11:361-79. 2010
    ..Clinical trials in patients with malignancies are being conducted. The use of VPA prior to or together with anticancer drugs may thus prove a beneficial treatment...
  91. pmc Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib
    D Lecis
    Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milano, Italy
    Br J Cancer 102:1707-16. 2010
  92. ncbi In vitro and in vivo efficacy of tribendimidine and its metabolites alone and in combination against the hookworms Heligmosomoides bakeri and Ancylostoma ceylanicum
    Lucienne Tritten
    Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
    Acta Trop 122:101-7. 2012
    ..19). In conclusion, tribendimidine and dADT show potent anti-hookworm properties. The potential of the promising tribendimidine-levamisole combination should be investigated in greater detail...
  93. ncbi 1'S-1'-acetoxyeugenol acetate: a novel phenylpropanoid from Alpinia conchigera enhances the apoptotic effects of paclitaxel in MCF-7 cells through NF-κB inactivation
    Lionel Lian Aun In
    Department of Genetics and Molecular Biology, Institute of Biological Science, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
    Anticancer Drugs 22:424-34. 2011
    ..conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies...
  94. pmc Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis
    Ling Gu
    Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
    J Exp Clin Cancer Res 29:150. 2010
    ..In this study we investigate the potential and mechanism of using rapamycin to restore the sensitivity of GC-resistant T-ALL cells to dexamethasone (Dex) treatment...
  95. pmc Bortezomib enhances the efficacy of fulvestrant by amplifying the aggregation of the estrogen receptor, which leads to a proapoptotic unfolded protein response
    Yuki Ishii
    Division of Hematology Oncology, Tisch Cancer Institute and Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA
    Clin Cancer Res 17:2292-300. 2011
    ..We tested whether combining fulvestrant with the proteasome inhibitor, bortezomib, could enhance the accumulation of ER aggregates and cause apoptotic cell death...
  96. pmc Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer
    Savita Bisht
    The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Mol Cancer Ther 9:2255-64. 2010
    ..NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy...
  97. ncbi Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells
    Mitsuru Miyachi
    Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
    Clin Cancer Res 15:4077-84. 2009
    ..In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines...
  98. ncbi The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia
    K D Mason
    Divisions of Cancer and Haematology and Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    Leukemia 23:2034-41. 2009
    ..These data indicate that combination of ABT-737 with a second anti-leukemic agent would improve response rates and suggest a potential role for combination therapies that include BH3 mimetics for the treatment of this disease...
  99. ncbi Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 6:1951-61. 2007
    ..Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412...
  100. ncbi The phage K lytic enzyme LysK and lysostaphin act synergistically to kill MRSA
    Stephen C Becker
    Animal Biosciences and Biotechnology Laboratory, Animal and Natural Resources Institute, Agricultural Research Service U S Department of Agriculture, Beltsville Agricultural Research Center, 10300 Baltimore Avenue, Beltsville, MD 20705, USA
    FEMS Microbiol Lett 287:185-91. 2008
    ..3-0.5 M NaCl), and C-His-LysK MIC (32.85+/-4.87 mug mL(-1)). LysK and lysostaphin demonstrate antimicrobial synergy by the checkerboard assay...
  101. ncbi Synergistic fungicidal activity of Cu(2+) and allicin, an allyl sulfur compound from garlic, and its relation to the role of alkyl hydroperoxide reductase 1 as a cell surface defense in Saccharomyces cerevisiae
    Akira Ogita
    Institute for Health and Sport Sciences, Osaka City University, 3 3 138 Sugimoto, Sumiyoshi ku, Osaka 558 8585, Japan
    Toxicology 215:205-13. 2005
    ..Our study suggests that allicin influences the mode of cell surface localization or the related function of AHP1 as a defense against phospholipid peroxidation by the external action of Cu(2+)...

Research Grants86

    Noah Syroid; Fiscal Year: 2005
    ..anesthesiologists are able to visualize model-predicted concentrations, effects and interactions due to drug-drug synergism. Preliminary studies have shown significant promise for this technology; time to wake-up after surgery was ..
  2. Amine N-Oxygenation by FMO3 and FMO4
    John Cashman; Fiscal Year: 2005
    ..Such fundamental information will be useful in the development of safer drugs, the prevention of adverse drug reactions and the protection of humans from disease. ..
  3. New Opioids for Alcoholism
    John Cashman; Fiscal Year: 2006
    ..The potential commercial application of the work is that the research could lead to a 'blockbuster' drug product. [unreadable] [unreadable]..
    John Cashman; Fiscal Year: 2001
    ..The study will provide an understanding of the structural and pharmaceutical properties of hDAT antagonists. The work will lead to new insight into the preparation of human medications necessary in the cessation of cocaine abuse. ..
  5. Aging Disease--Prion/Transgenic/Immunologic Studies
    Michael Oldstone; Fiscal Year: 2008
    ..Lastly, Jose Criado will continue his electrophysiology and behavioral studies on the normal function of PrP and on its aberrations during TSE disease. ..
  6. Effects of Chinese Herbal Medicines on Allergic Asthma
    Xiu Min Li; Fiscal Year: 2003
    ..Accomplishing these goals should provide an experimental basis for applying Chinese herbal medicines to the treatment of allergic asthma, and for understanding immunoregulatory mechanisms underlying their effects. ..
  7. Biochemical Characterization of Opioid Receptors
    Gavril W Pasternak; Fiscal Year: 2010
    ..Together, these studies should give a better understanding of the actions of opioids and their pharmacology. ..
  8. Mitochondria Targeted Anti-oxidant for Treatment of Prostate Cancer
    HIRAK BASU; Fiscal Year: 2008
    ..Here, we propose Phase I SBIR pre- clinical studies necessary to identify the lead drug candidate and develop as a clinically useful anti-prostate cancer drug. [unreadable] [unreadable] [unreadable]..
    Daniel Javitt; Fiscal Year: 2005
    ..This study will evaluate neurophysiological and neurochemical hypotheses concerning potential etiology of early sensory processing dysfunction in schizophrenia. ..
  10. DNA and Phytochemical Fingerprinting of Actaea Species
    Edward Kennelly; Fiscal Year: 2007
    ..Our long-range goals are to improve the quality of black cohosh dietary supplements and understand the variation in Actaea species. ..
  11. Separate and Combined Effects of Progesterone and Triazolam in Healthy Women
    Shanna Babalonis; Fiscal Year: 2008
    ..As such, these studies will contribute towards the development of gender-specific intervention and/or prevention strategies and health management approaches. [unreadable] [unreadable] [unreadable]..
  12. Psychostimulants and Alpha-1 Adrenoceptor Subtypes
    Paul Wellman; Fiscal Year: 2006
    ..These studies will advance our understanding of the behavioral functions of brain a l-AR subtypes and may lead to the identification of new drugs that inhibit eating without activating brain reinforcement systems. ..
  13. Angiotensin II Mediates Early Changes in Diabetic Kidney
    Helmy Siragy; Fiscal Year: 2007
    ..The proposed studies will help understand the mechanisms that are involved in diabetic the development of new therapeutic modalities to prevent or slowdown the development ..
    KARL WITTRUP; Fiscal Year: 2001
    DAVID CULP; Fiscal Year: 2001
    ..Results will provide specific information for determination of the dose and temporal administration of agonist in future clinical trials to treat patients with salivary hypofunction. ..
  16. Combined Natural Inhibitors in Skin Cancer Prevention
    THOMAS SLAGA; Fiscal Year: 2007
    ..abstract_text> ..
  17. Silibinin in Prostate Cancer Chemoprevention & Treatment
    Michael Pollak; Fiscal Year: 2004
    ..The work is justified by the favorable toxicity profile of silibinin, together with prior positive laboratory studies reported by our group and other investigators. ..
  18. Viruses and Diabetes
    Michael Oldstone; Fiscal Year: 2005
    NISSAR DARMANI; Fiscal Year: 2007
    ..The results will have important implications for the therapeutic utility of these "agonist antiemetics". [unreadable] [unreadable]..
  20. Pain Regulatory Dysfunction in Chronic Pain
    Stephen Bruehl; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  21. Targeted Proteomics of Stress and Addiction
    KATHRYN CUNNINGHAM; Fiscal Year: 2005
    ..abstract_text> ..
  22. Engineering and Analysis of T cell CD3 and IL2R Signals
    KARL WITTRUP; Fiscal Year: 2008
    ..These studies will provide insights into T cell regulation as well as develop CDS and IL-2 stimulatory molecules of potential therapeutic value. ..
  23. Locomotion Control by Lumbar Spinal Cord Stimulation
    Changfeng Tai; Fiscal Year: 2008
    ..The proposed studies will not only improve our understanding of locomotion control in lumbar spinal cord but also benefit SCI patients. ..
  24. Role of Glutamate in Opiate Tolerance and Sensitization
    KEITH TRUJILLO; Fiscal Year: 2005
    ..abstract_text> ..
  25. Gene delivery to striated muscle by systemic AAV vectors
    Dwight D Koeberl; Fiscal Year: 2010
    ..Efficacious muscle-targeted gene therapy in GSD-II will have implications for gene therapy in other muscular dystrophies and myopathies. ..
  26. Antihyperlipidemic Effects of Oyster Mushrooms
    Donald Abrams; Fiscal Year: 2004
    ..abstract_text> ..
  27. Pathogenesis Studies in Scrapie (TSE Diseases)
    Michael Oldstone; Fiscal Year: 2003
    ..This model should be useful to study pathophysiology of CWD as well as probing CWD strain differences. ..
    Kimberly Foreman; Fiscal Year: 2002
    ..Such new treatment options are important for AIDS patients who frequently develop this deadly neoplasm. ..
    NISSAR DARMANI; Fiscal Year: 2001
    ..The results will define an important role for the cannabinoid receptors in the vomiting circuits and may implicate an antiemetic role for the endogenous cannabinoids. ..
    OSKAR FRANKFURT; Fiscal Year: 2002
  31. Roles of Neuregulin-1 in Age Related Neuronal Changes
    Jianxin Bao; Fiscal Year: 2009
    ..The ultimate goal of our research is to develop methods for prevention and treatment of age related functional decline of nervous system based on identifying molecular candidates involved in the aging process ..
  32. Mechanisms for immune tolerance in Pompe Disease
    Dwight D Koeberl; Fiscal Year: 2010
    ..These comparisons will guide preclinical experiments to further immunomodulatory gene therapy in Pompe disease and other lysosomal storage disorders. ..
    Bonnie Ramsey; Fiscal Year: 2003
    ..abstract_text> ..
  34. Effect of Chinese herbal medicine on food allergy
    Xiu Min Li; Fiscal Year: 2010
  35. GR Impairment in Carconogenesis: Tumor Suppressor Role
    THOMAS SLAGA; Fiscal Year: 2009
    ..4) To analyze the effects of dissociated glucocorticoids on skin inflammation, keratinocyte proliferation, and on skin tumor development. ..
    Michael Oldstone; Fiscal Year: 2001
    ..The second order of business is to determine the role of "self" (islet-cell) antigens other than the initial triggering viral antigen in the pathogenetic process leading to and determine their role in IDDM. ..
    Ronald Tallarida; Fiscal Year: 2004
    ..This guide is the newest aim of this revised application. ..
    CYNTHIA WENNER; Fiscal Year: 2004
    ..By addressing these aims, Dr. Wenner will gain strong research skills in botanical medicine and the expertise necessary to significantly impact this field. ..
  39. Apoptotic Mechanisms of Tocotrienols in Mammary Cancer
    Paul Sylvester; Fiscal Year: 2004
    ..Although caspase-8 activation is associated with death receptor signaling, the exact receptor/ligand signaling mechanism(s) mediating tocotrienol-induced caspase-8 activation has not been determined. ..
    Stephen Bruehl; Fiscal Year: 2002
    ..Greater pain duration is expected to be associated with smaller changes in the BP/pain relationship in response to opioid blockade. ..
  41. Reactive astrocytes from gliotic capsule
    J Marc Simard; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  42. Therapeutics to Prevent/Treat Lassa Fever Virus
    Michael B Oldstone; Fiscal Year: 2010
    ..We anticipate making a significant contribution to drug development to treat these BSL-4 agents. ..
  43. Novel Active Repressor Model of Human LDL-Receptor Regulation
    Johannes Veldhuis; Fiscal Year: 2008
    ..This would represent a new treatment approach for patients with atherosclerotic disease. [unreadable] [unreadable] [unreadable] [unreadable]..
    Donna M Lehman; Fiscal Year: 2010
    ..5 LOD support interval. Furthermore, the utilization of a novel statistical functional genomic analysis (Bayesian quantitative trait nucleotide analysis) should enhance the final stage of identifying the specific variants involved. ..
  45. Phencyclidine Abuse & Psychosis: Biomedical Mechanisms
    Daniel C Javitt; Fiscal Year: 2010
  46. Synergistic activation of PTGS2 and CXCL8 by Ni and microbial stimuli
    Kelly Brant; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
    Kathryn A Cunningham; Fiscal Year: 2010
  48. Ensemble Disruption of the GnRH-LH-Testosterone Axis
    Johannes Veldhuis; Fiscal Year: 2007
    ..Expected corollary outcomes are enhanced diagnosis, assessment and management of more subtle pathophysiology of the male gonadal axis in puberty and adulthood. ..
    KATHRYN CUNNINGHAM; Fiscal Year: 2005
    ..abstract_text> ..
  50. Analytical Reconstruction of Feedback Signaling in Aging Men
    Johannes Veldhuis; Fiscal Year: 2008
    ..The present proposal develops a general biomathematical framework for dissecting otherwise observed pathways that control hormone output in aging, stress and disease. [unreadable] [unreadable] [unreadable]..
  51. Targeting Notch and Tyrosine Kinase Receptors in Ks
    Kimberly Foreman; Fiscal Year: 2005
    ..abstract_text> ..
    Daniel Javitt; Fiscal Year: 2006
    ..The research will build upon studies currently supported by NIH research and career development awards to the candidate, and will permit the candidate to continue to devote >75 percent effort to research. ..
  53. Molecular Mechanisms Underlying Age-Related Hearing Loss
    Jianxin Bao; Fiscal Year: 2004
    ..The ultimate goal of this research is to develop methods for prevention and treatment of age-related loss of SGNs, based on identifying molecular candidates involved in this aging process. ..
    Michael Oldstone; Fiscal Year: 2007
    ..abstract_text> ..
    Alan Eastman; Fiscal Year: 2007
    ..The ultimate goal of this research program will be to define which pathway and effector a specific leukemia uses, and then prescribe effective drug combinations that will be individualized for that patient. ..
    Alan Eastman; Fiscal Year: 2001
    ..These experiments should identify a drug combination that can be tested for its selective targeting to p53-defective tumors in future clinical trials. ..
  57. Prostate-Directed Antioxidant to Prevent Prostate Cancer
    HIRAK BASU; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    Fredika Robertson; Fiscal Year: 2001
    ..The hypothesis driving this research is that NO and peroxynitrite are mutagenic, and could be important contributors to oxidative DNA damage and mutation in human epidermal keratinocytes at sites of inflammation. ..
    Johannes Veldhuis; Fiscal Year: 2005
    ..Understanding such fundamental interactions is important to the rational design of alternative strategies to interrupt normal and rescue impaired steroidogenesis in the maturing Graafian follicle and corpus luteum. ..
    John Osborn; Fiscal Year: 2007
    ..Taken together, this integrative physiological approach will advance our understanding of the neural mechanisms for long-term control of arterial pressure and pathogenesis of neurogenic hypertension. [unreadable] [unreadable]..
  61. AT2 Receptor Modulates Renal Angiotensin II Levels
    Helmy Siragy; Fiscal Year: 2005
    ..Data obtained from this proposal will lead to increased understanding of the pathophysiology of hypertension and development of novel therapies for its management. ..
  62. Efficacy of 25-hydroxyvitamin D3 in colon cancer chemoprevention
    Rajendra G Mehta; Fiscal Year: 2010
    ..The studies will provide a rationale for using 25(OH)D3 for the prevention of colon carcinogenesis. ..
  63. Opioid and Cannabinoid Pharmacokinetic Interactions
    Donald Abrams; Fiscal Year: 2007
    ..Nausea and vomiting will be assessed daily via self-report. The study will be conducted over a 2-year period. [unreadable] [unreadable] [unreadable]..
  64. Modulation of Tumor CEA Levels for an Anti-CEA Vaccine
    William Carson; Fiscal Year: 2006
    ..These analyses will allow us to determine whether the expression of the CEA tumor antigen can be modulated by cytokine treatment and if this translates into an improved anti-tumor response. ..
  65. TNF Blockade in Pancreatic Cancer Patients
    MIGUEL VILLALONA; Fiscal Year: 2004
    ..The observation of benefits in either quality of life or progression-free survival in patients undergoing TNF blockade would encourage evaluation of this novel strategy in properly powered randomized clinical trials. ..
  66. Fetal & Adolescent Nicotine Effects on CNS 5HT Systems
    Theodore Slotkin; Fiscal Year: 2003
    ..abstract_text> ..
  67. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  68. Novel Antifungal Strategies for Lethal Mucormycosis
    Ashraf Ibrahim; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  69. Urokinase-type Plasminogen Activator System and Pancreatic Stellate Cells
    Aurelia Lugea; Fiscal Year: 2007
    ..Therapeutic strategies focusing on the regulation of uPA activation may be central in preventing or reverting alcohol-induced pancreas fibrosis. [unreadable] [unreadable] [unreadable]..
  70. Androgen deficiency and Osteopenia in Anorexia Nervosa
    Karen Miller; Fiscal Year: 2002
    ..In the third phase of the study, we will examine the effects of administering testosterone on bone density and body mass. ..
  71. Chemoprevention of murine urinary bladder carcinogenesis
    Ashish Kamat; Fiscal Year: 2005
    ..abstract_text> ..
  72. Therapy of Melanoma with Bortezomib and Interferon-alpha
    William Carson; Fiscal Year: 2007
    ..These studies will help to define the specific apoptotic and immunostimulatory pathways that are being modulated by the combination of bortezomib and IFN-a2b. [unreadable] [unreadable]..
  73. Focusing oral health research at the University of Iowa
    Christopher Squier; Fiscal Year: 2003
    ..abstract_text> ..
    Christopher Squier; Fiscal Year: 2002
  75. Tumor suppressor adenomatous polyposis coli and breast carcinogenesis
    Satya Narayan; Fiscal Year: 2007
  76. Exposure to beef growth promoter in breast cancer
    YOUNG LIN; Fiscal Year: 2003
    Satya Narayan; Fiscal Year: 2001
    ..Therefore, novel therapeutic strategies may emerge with respect to potential new targets for chemotherapeutic intervention in colon cancer. ..
  78. Phase1/11 study of 5-aza-2'-deoxycytidine and valproic *
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..Decitabine will be generously provided by SuperGen (r). Valproic acid is an FDA approved anti-convulsant. ..
  79. Muller glia and neuronal regeneration in the retina
    Andy Fischer; Fiscal Year: 2009
    ..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..
    Mary Lampe; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  81. New Target For Stroke: Peroxisome Proliferator Activated Receptor-Gamma
    Jaroslaw Aronowski; Fiscal Year: 2008
    ..3. To evaluate optimal conditions (selection of drug, dose, time window for effective treatment, tolerance, and effectiveness in permanent vs. reversible ischemia) for the anti-ischemic activity of PPARy agonists. ..
  82. Studying nicotinic AChRs in histaminergic neurons
    VICTOR UTESHEV GAARD; Fiscal Year: 2007
    ..Some of these effects of nicotine and therapeutic nicotinic agents may arise from their ability to modulate histaminergic function. [unreadable] [unreadable]..
  83. Cell Cycle Controlling Genes in Adult Acute Lymphoma
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..abstract_text> ..
    Yung Chi Cheng; Fiscal Year: 2007
    ..It should yield novel information for understanding the biochemical determinants of the action of L-OddC, the biochemistry of the enzymes studied and possible novel use of L-OddC for the treatment of solid tumor. ..