antineoplastic antimetabolites

Summary

Summary: Antimetabolites that are useful in cancer chemotherapy.

Top Publications

  1. ncbi 5-fluorouracil: mechanisms of action and clinical strategies
    Daniel B Longley
    Cancer Research Centre, Department of Oncology, Queen s University Belfast, University Floor, Belfast City Hospital, 97 Lisburn Road, Belfast BT9 7AB, Northern Ireland
    Nat Rev Cancer 3:330-8. 2003
  2. ncbi Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial
    Helmut Oettle
    Department of Medical Oncology and Hematology, Charite School of Medicine, Campus Virchow Klinikum, Berlin, Germany
    JAMA 297:267-77. 2007
  3. ncbi Development and characterization of gemcitabine-resistant pancreatic tumor cells
    Ami N Shah
    Department of Surgical Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Ann Surg Oncol 14:3629-37. 2007
  4. ncbi Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death
    Alexander Arlt
    1Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Medicine, University of Kiel, Germany
    Oncogene 22:3243-51. 2003
  5. ncbi Capecitabine as adjuvant treatment for stage III colon cancer
    Chris Twelves
    University of Leeds and Bradford NHS Hospitals Trust, Leeds, United Kingdom
    N Engl J Med 352:2696-704. 2005
  6. pmc Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer
    Christine M Ribic
    Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto
    N Engl J Med 349:247-57. 2003
  7. ncbi Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction
    J S Macdonald
    St Vincent's Comprehensive Cancer Center, New York, USA
    N Engl J Med 345:725-30. 2001
  8. ncbi An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines
    Jennifer D Davidson
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
    Cancer Res 64:3761-6. 2004
  9. ncbi Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene
    Kazuyuki Kawakami
    Department of Surgery, Kanazawa University School of Medicine, Kanazawa 920 8641, Japan
    Cancer Res 63:6004-7. 2003
  10. ncbi A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer
    John P Neoptolemos
    Department of Surgery, Liverpool University, Liverpool, United Kingdom
    N Engl J Med 350:1200-10. 2004

Research Grants

Detail Information

Publications308 found, 100 shown here

  1. ncbi 5-fluorouracil: mechanisms of action and clinical strategies
    Daniel B Longley
    Cancer Research Centre, Department of Oncology, Queen s University Belfast, University Floor, Belfast City Hospital, 97 Lisburn Road, Belfast BT9 7AB, Northern Ireland
    Nat Rev Cancer 3:330-8. 2003
    ..Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy...
  2. ncbi Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial
    Helmut Oettle
    Department of Medical Oncology and Hematology, Charite School of Medicine, Campus Virchow Klinikum, Berlin, Germany
    JAMA 297:267-77. 2007
    ..The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists...
  3. ncbi Development and characterization of gemcitabine-resistant pancreatic tumor cells
    Ami N Shah
    Department of Surgical Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Ann Surg Oncol 14:3629-37. 2007
    ..To study the mechanisms of chemoresistance in pancreatic cancer we developed two gemcitabine-resistant pancreatic cancer cell lines...
  4. ncbi Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death
    Alexander Arlt
    1Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Medicine, University of Kiel, Germany
    Oncogene 22:3243-51. 2003
    ....
  5. ncbi Capecitabine as adjuvant treatment for stage III colon cancer
    Chris Twelves
    University of Leeds and Bradford NHS Hospitals Trust, Leeds, United Kingdom
    N Engl J Med 352:2696-704. 2005
    ..The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting...
  6. pmc Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer
    Christine M Ribic
    Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto
    N Engl J Med 349:247-57. 2003
    ..We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer...
  7. ncbi Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction
    J S Macdonald
    St Vincent's Comprehensive Cancer Center, New York, USA
    N Engl J Med 345:725-30. 2001
    ..CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection...
  8. ncbi An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines
    Jennifer D Davidson
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
    Cancer Res 64:3761-6. 2004
    ..The results from this study indicate that the level of RRM1 may affect gemcitabine response. Furthermore, RRM1 may serve as a biomarker for gemcitabine response...
  9. ncbi Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene
    Kazuyuki Kawakami
    Department of Surgery, Kanazawa University School of Medicine, Kanazawa 920 8641, Japan
    Cancer Res 63:6004-7. 2003
    ..These results suggest that the double polymorphism in the TS tandem repeat sequence, the SNP and the VNTR, may provide a potential for more effective prediction of the clinical outcome of 5-fluorouracil-based chemotherapy...
  10. ncbi A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer
    John P Neoptolemos
    Department of Surgery, Liverpool University, Liverpool, United Kingdom
    N Engl J Med 350:1200-10. 2004
    ..The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results...
  11. ncbi Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism
    G J Peters
    Department of Medical Oncology, VU University Medical Center, P O Box 7057, 1007 MB, Amsterdam, The Netherlands
    Biochim Biophys Acta 1587:194-205. 2002
    ..The clear retrospective relation between TS levels and response now forms the basis for a prospective study, in which TS levels are measured before treatment in order to determine the treatment protocol...
  12. pmc Meta-analysis on inoperable pancreatic cancer: a comparison between gemcitabine-based combination therapy and gemcitabine alone
    De Rong Xie
    Department of Oncology, Second Affiliated Hospital, Sun Yat Sen University, Guangzhou 510120, Guangdong Province, China
    World J Gastroenterol 12:6973-81. 2006
    ..To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta-analysis...
  13. ncbi Evaluation of a 7-day continuous intravenous infusion of decitabine: inhibition of promoter-specific and global genomic DNA methylation
    Wolfram E Samlowski
    Huntsman Cancer Institute and the Department of Internal Medicine Oncology, University of Utah, Salt Lake City, UT 84112 5550, USA
    J Clin Oncol 23:3897-905. 2005
    ..A clinical study was designed to examine the molecular effects and toxicity of a continuous 1-week intravenous infusion of decitabine in solid tumor patients...
  14. ncbi Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy
    Thierry Lecomte
    Service de Gastroenterologie, Assistance Publique Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris
    Clin Cancer Res 10:5880-8. 2004
    ..The aim of this study was to investigate the utility of determining these two TYMS gene polymorphisms to predict the toxicity and efficacy of 5-FU treatment in patients with colorectal cancer...
  15. ncbi Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Stuttgart, Stuttgart, Germany
    J Clin Oncol 26:2131-8. 2008
    ....
  16. pmc Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
    Ana M Mendes-Pereira
    The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
    EMBO Mol Med 1:315-22. 2009
    ..The data we present here now suggests that the clinical assessment of PARP inhibitors should be extended beyond those with BRCA mutations to a larger group of patients with PTEN mutant tumours...
  17. ncbi Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy
    Anna K Nowak
    Western Australian Institute for Medical Research, University Department of Medicine, Queen Elizabeth II Medical Centre, 4th Floor, G Block, Nedlands, Perth, Western Australia 6009
    Cancer Res 62:2353-8. 2002
    ..In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine...
  18. ncbi DNA methylation and gene silencing in cancer
    Stephen B Baylin
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Nat Clin Pract Oncol 2:S4-11. 2005
    ..This review examines alteration in DNA methylation in cancer, effects on gene expression, and implications for the use of hypomethylating agents in the treatment of cancer...
  19. ncbi Phase I study of continuous-infusion L-S,R-buthionine sulfoximine with intravenous melphalan
    H H Bailey
    Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison 53792, USA
    J Natl Cancer Inst 89:1789-96. 1997
    ....
  20. ncbi Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project
    L Crino
    Department of Medical Oncology, Policlinico Hospital, Perugia, Italy
    J Clin Oncol 17:3522-30. 1999
    ..The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity...
  21. ncbi CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial
    Viviane Hess
    Division of Medical Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
    Lancet Oncol 9:132-8. 2008
    ....
  22. ncbi Potential mechanisms of resistance to cytarabine in AML patients
    Carlos M Galmarini
    Unité INSERM 453, Laboratoire de Cytologie Analytique, Faculte de Medecine Rockefeller, 8, avenue Rockefeller, 69373 Lyon Cedex 08, France
    Leuk Res 26:621-9. 2002
    ..These results suggest that expression of 5NT and reduced hENT1 in leukemic blasts at diagnosis are correlated with clinical outcome and may play a role in resistance mechanisms to ara-C in patients with AML...
  23. pmc Intrinsic chemoresistance to gemcitabine is associated with constitutive and laminin-induced phosphorylation of FAK in pancreatic cancer cell lines
    Wu Huanwen
    Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, PR China
    Mol Cancer 8:125. 2009
    ..In this study, we aimed to determine the roles of FAK phosphorylation in the intrinsic chemoresistance of pancreatic cancer cell lines...
  24. ncbi Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine
    Shinichi Sakuramoto
    Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
    N Engl J Med 357:1810-20. 2007
    ..Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer...
  25. ncbi DNA microarray analysis of the correlation between gene expression patterns and acquired resistance to 5-FU/cisplatin in gastric cancer
    Hark Kyun Kim
    Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
    Biochem Biophys Res Commun 316:781-9. 2004
    ..These exploratory data demonstrate that the gene expression profiles differ between chemosensitive and refractory state gastric cancer biopsy samples...
  26. ncbi Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients
    Rafael Rosell
    Medical Oncology Service, Institut Catala d Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain
    Clin Cancer Res 10:1318-25. 2004
    ..Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity...
  27. ncbi Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297
    Jordan D Berlin
    Vanderbilt University, 777 Preston Research Building, Nashville, TN 37232 6307, USA
    J Clin Oncol 20:3270-5. 2002
    ....
  28. pmc Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fluoropyrimidine-related toxicity in cancer patients
    Eva Gross
    Department of Gynecology, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany
    PLoS ONE 3:e4003. 2008
    ..As known deleterious mutations explain only a limited proportion of the drug-adverse events, we systematically searched for additional DPYD variations associated with enhanced drug toxicity...
  29. ncbi Resistance of colon cancer cells to long-term 5-fluorouracil exposure is correlated to the relative level of Bcl-2 and Bcl-X(L) in addition to Bax and p53 status
    Sabine Violette
    INSERM U505, Universite Pierre et Marie Curie, Paris, France
    Int J Cancer 98:498-504. 2002
    ..In conclusion, the relative levels of Bcl-2, Bcl-x(L) and Bax may altogether contribute to determine the resistance of a majority of colon tumor cells to long-term 5-FU treatment, whatever their p53 status...
  30. ncbi A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells
    Mark S Duxbury
    Department of Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 64:3987-93. 2004
    ..Differential expression of CEACAM6 modulates Akt activity in a c-Src-dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis...
  31. ncbi Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer
    Dae Yong Kim
    Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
    Int J Radiat Oncol Biol Phys 67:378-84. 2007
    ..To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer...
  32. ncbi Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients
    Hany H Ezzeldin
    Division of Clinical Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294 3300, USA
    Clin Cancer Res 11:8699-705. 2005
    ..The current study investigates the role of methylation in cancer patients with an unexplained molecular basis of DPD deficiency...
  33. pmc Pharmacogenomics of gemcitabine: can genetic studies lead to tailor-made therapy?
    H Ueno
    Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5 1 1 Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    Br J Cancer 97:145-51. 2007
    ..In this paper, we review recent genetic studies of gemcitabine, and discuss the possibility of individualised cancer chemotherapy based on a pharmacogenomic approach...
  34. ncbi Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial
    Michele Reni
    Department of Radiochemotherapy, S Raffaele H Scientific Institute, Milan, Italy
    Lancet Oncol 6:369-76. 2005
    ..We aimed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone...
  35. pmc A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer
    S R Bramhall
    Department of Surgery, Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
    Br J Cancer 87:161-7. 2002
    ..The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified...
  36. ncbi Gemcitabine-based combinations for inoperable pancreatic cancer: have we made real progress? A meta-analysis of 20 phase 3 trials
    Emilio Bria
    Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy
    Cancer 110:525-33. 2007
    ..Several attempts have been made at improving the efficacy of gemcitabine in advanced pancreatic cancer by combining it with other chemotherapeutic or molecularly targeted agents. However, randomized trials have produced conflicting results...
  37. ncbi Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer
    Jun Sang Kim
    Department of Therapeutic Radiology, College of Medicine, Chungnam National University, Jung Gu, Taejon, South Korea
    Int J Radiat Oncol Biol Phys 54:403-8. 2002
    ..We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer...
  38. ncbi Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation
    Andre B P van Kuilenburg
    Emma Children s Hospital and Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, The Netherlands
    Int J Cancer 101:253-8. 2002
    ....
  39. ncbi Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration
    Hany Ezzeldin
    Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294 3300, USA
    Clin Colorectal Cancer 4:181-9. 2004
    ..The variability of DPD enzyme activity in population studies and the different DPYD alleles together with new phenotypic and genotypic methods of screening for DPD deficiency will also be reviewed...
  40. ncbi Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis
    Ker Y Cheah
    Disciplines of Wine and Horticulture, School of Agriculture, Food and Wine, University of Adelaide, Adelaide, South Australia
    Cancer Biol Ther 8:382-90. 2009
    ..GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis...
  41. ncbi CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer
    Marius van Rijnsoever
    Departments of Surgery, University of Western Australia, Nedlands 6907, Australia
    Clin Cancer Res 9:2898-903. 2003
    ..The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months...
  42. ncbi Meta-analysis of randomised trials comparing gemcitabine-based doublets versus gemcitabine alone in patients with advanced and metastatic pancreatic cancer
    Eugeniu Banu
    Medical Oncology Department, Georges Pompidou European Hospital, Paris, France
    Drugs Aging 24:865-79. 2007
    ..To evaluate the impact on overall survival at 6, 12 and 18 months of gemcitabine-based doublets compared with gemcitabine alone in patients with advanced and metastatic pancreatic cancer...
  43. ncbi In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression
    Axel Rainer Hanauske
    Asklepios Klinik, St Georg, Lohmühlenstr 5, 20099 Hamburg, Germany
    Invest New Drugs 25:417-23. 2007
    ..mRNA expression of genes involved in the mechanism of action of pemetrexed was correlated with in vitro chemosensitivity of freshly explanted human tumor specimens...
  44. pmc Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2
    Sarah A Martin
    Cancer Research UK Gene Function and Regulation Group, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
    EMBO Mol Med 1:323-37. 2009
    ..While methotrexate has been used for many years as a cancer therapy, our observations suggest that this drug may have particular utility for the treatment of a subset of patients with tumours characterized by MSH2 mutations...
  45. ncbi The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells
    C Flotho
    Division of Pediatric Hematology Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
    Leukemia 23:1019-28. 2009
    ....
  46. ncbi Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study
    Jean Philippe Spano
    Hopital de la Pitie Salpetriere, Paris, France
    Lancet 371:2101-8. 2008
    ..The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone...
  47. ncbi Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study
    A De Paoli
    Department of Radiation Oncology, C R O National Cancer Institute, Aviano, Italy
    Ann Oncol 17:246-51. 2006
    ..The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer...
  48. ncbi Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205)
    Atsushi Ohtsu
    Division of Gastrointestinal Oncology Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
    J Clin Oncol 21:54-9. 2003
    ..To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial...
  49. ncbi Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate
    Jean Pierre J Issa
    Department of Leukemia and Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 23:3948-56. 2005
    ..To determine the activity of decitabine, a DNA methylation inhibitor, in imatinib-refractory or intolerant chronic myelogenous leukemia...
  50. pmc Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery
    Paula M De Angelis
    Institute of Pathology, Section for Molecular Chemoresistance, Rikshospitalet Radiumhospitalet HF, Oslo, Norway
    Mol Cancer 5:20. 2006
    ....
  51. ncbi Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats
    T Takechi
    Anticancer and Antimicrobials Research Laboratory, Taiho Pharmaceutical Co Ltd, Tokushima, Japan
    Cancer Chemother Pharmacol 39:205-11. 1997
    ....
  52. ncbi Topical therapy for actinic keratoses, I: 5-Fluorouracil and imiquimod
    William D Tutrone
    University of Vermont, Burlington, USA
    Cutis 71:365-70. 2003
    ..Therapies include 5-fluorouracil, imiquimod, diclofenac, colchicine, and retinoids. The first part of this review will focus on topical 5-fluorouracil and imiquimod...
  53. ncbi Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate
    Caio M Rocha Lima
    University of Miami and Sylvester Cancer Center, Miami, FL 33162, USA
    J Clin Oncol 22:3776-83. 2004
    ....
  54. ncbi Current understanding of methotrexate pharmacology and efficacy in acute leukemias. Use of newer antifolates in clinical trials
    G S Longo-Sorbello
    Divisione di Ematologia, Centro di Riferimento Oncologico, Ospedale S Vincenzo, Contrada Sirina, 98039 Taormina, Italy
    Haematologica 86:121-7. 2001
    ..This information may improve the use of MTX or could lead to the development of better drugs. Moreover a short description of newer antifolates with their mechanisms of action is presented...
  55. ncbi Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial
    Joseph Jorizzo
    Department of Dermatology, Clinical Sciences Building 9th Floor, Wake Forest University School of Medicine, Winston Salem, NC 27157 1071, USA
    Arch Dermatol 140:813-6. 2004
    ..No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis...
  56. ncbi Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study
    Christos Kosmas
    Department of Medicine, 2nd Division of Medical Oncology, Metaxa Cancer Hospital, Piraues, 21 Apolloniou Street, 16341 Athens, Greece
    J Cancer Res Clin Oncol 134:75-82. 2008
    ..In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration...
  57. ncbi Ribonucleotide reductase subunit M2 mRNA expression in pretreatment biopsies obtained from unresectable pancreatic carcinomas
    Takao Itoi
    Fourth Department of Internal Medicine, Tokyo Medical University, 6 7 1 Nishishinjuku, Tokyo 160 0023, Japan
    J Gastroenterol 42:389-94. 2007
    ..Recently, gemcitabine resistance has been associated with the ribonucleotide reductase subunit M2 (RRM2). In this prospective study, we hypothesized that RRM2 expression in PC biopsy specimens would be a significant predictor of outcome...
  58. ncbi A single-institution experience with concurrent capecitabine and radiation therapy in gastrointestinal malignancies
    U N Vaishampayan
    Department of Internal Medicine, Division of Oncology, The Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA
    Int J Radiat Oncol Biol Phys 53:675-9. 2002
    ..We report our clinical experience with 32 patients receiving concurrent irradiation and capecitabine...
  59. ncbi High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial
    Andres J M Ferreri
    Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy
    Lancet 374:1512-20. 2009
    ..We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma...
  60. ncbi Treatment of advanced hepatocellular carcinoma with biweekly high-dose gemcitabine
    H Ulrich-Pur
    Department of Internal Medicine I, Division of Oncology, Vienna University Medical School, Vienna, Austria
    Oncology 60:313-5. 2001
    ....
  61. ncbi Altered expression of Ape1/ref-1 in germ cell tumors and overexpression in NT2 cells confers resistance to bleomycin and radiation
    K A Robertson
    Herman B. Wells Center for Pediatric Research, Department of Pediatrics, James Whircomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis 46202, USA
    Cancer Res 61:2220-5. 2001
    ..To our knowledge, this is the first example of overexpressing Ape1/ref-1 in a mammalian system resulting in enhanced protection to DNA-damaging agents...
  62. ncbi Transcriptional regulation of aldo-keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis
    Elisabet Selga
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av Diagonal 643, E 08028 Barcelona, Spain
    Biochem Pharmacol 75:414-26. 2008
    ..Finally, overexpression of AKR1C1 in MTX sensitive HT29 cells conferred resistance to the chemotherapeutic agent and silencing of AKR1C1 by means of iRNA technology sensitized the cells to MTX...
  63. ncbi Effect of cytarabine and decitabine in combination in human leukemic cell lines
    Taichun Qin
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 13:4225-32. 2007
    ..5-Aza-2'-deoxycytidine (DAC) is a cytosine analogue that inhibits DNA methylation and also has activity in myeloid leukemia. Therefore, we investigated combining these two drugs in human leukemia cell lines in vitro...
  64. ncbi Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W
    P Vreken
    Academic Medical Center, University of Amsterdam, The Netherlands
    Hum Genet 101:333-8. 1997
    ..Only one of these patients showed convulsive disorders during childhood, whereas the other showed no clinical phenotype, further illustrating the lack of correlation between genotype and phenotype in DPD deficiency...
  65. ncbi Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity
    D R Rauchwerger
    Department of Pharmacology, University of Toronto, Ontario, Canada
    Cancer Res 60:6075-9. 2000
    ..This was also associated with a significant increase in es-NT levels caused by the TS inhibitors. Thus, modulation of the es-NT by pretreatment with TS inhibitors may have the potential to improve the therapeutic benefit of gemcitabine...
  66. pmc Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer
    M Tsukuda
    Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, Kanazawa Ku, Yokohama, Japan
    Br J Cancer 93:884-9. 2005
    ..0-92.4%); arm B 77.0% (95% CI: 65.0-89.0%). The schedule of 2-week administration followed by 1-week rest seems to be more feasible for oral 6-month administration of S-1 in adjuvant chemotherapy of locoregionally advanced SCCHN...
  67. pmc Phase II study of gemcitabine in patients with advanced pancreatic cancer
    J Carmichael
    ICRF Clinical Oncology Unit, Churchill Hospital, Oxford, UK
    Br J Cancer 73:101-5. 1996
    ..For these reasons and because of its novel mode of action, gemcitabine warrants further investigation in combination studies in pancreatic cancer...
  68. ncbi Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer
    Volker Heinemann
    Medizinische Klinik und Poliklinik III, Klinikum Grosshadern, Munich, Germany
    J Clin Oncol 24:3946-52. 2006
    ..To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer...
  69. ncbi New applications of gemcitabine and future directions in the management of pancreatic cancer
    James L Abbruzzese
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Cancer 95:941-5. 2002
    ....
  70. ncbi Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma
    P O'BRIEN
    Trans Tasman Radiation Oncology Group Department of Radiation Oncology, Newcastle Mater Hospital, Newcastle, New South Wales, Australia
    J Clin Oncol 18:519-26. 2000
    ..To assess, in a multi-institutional setting, the impact on relapse, survival, and toxicity of adding two cycles of intravenous methotrexate to cranial irradiation for immunocompetent patients with primary CNS lymphoma...
  71. pmc Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells
    Y Nakano
    Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan
    Br J Cancer 96:457-63. 2007
    ..The ratio of the four gene expression levels correlates with acquired gemcitabine-resistance in pancreatic cancer cells, and may be useful as a predictive marker for the efficacy of gemcitabine therapy in pancreatic cancer patients...
  72. ncbi The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma
    Jennifer Spratlin
    University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada
    Clin Cancer Res 10:6956-61. 2004
    ....
  73. pmc Time course of bleomycin-induced lung fibrosis
    G Izbicki
    Lung Cellular and Molecular Biology Laboratory Institute of Pulmonology, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem, Israel
    Int J Exp Pathol 83:111-9. 2002
    ..Computer-assisted morphometry provides objective and quantitative measurements that are a useful tool for the evaluation of bleomycin-induced lung injury...
  74. ncbi Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma
    G Boz
    Department of Radiotherapy, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
    Int J Radiat Oncol Biol Phys 51:736-40. 2001
    ..In this study, we report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma...
  75. ncbi Cellular elimination of 2',2'-difluorodeoxycytidine 5'-triphosphate: a mechanism of self-potentiation
    V Heinemann
    Department of Medical Oncology, University of Texas M D Anderson Cancer Center, Houston 77030
    Cancer Res 52:533-9. 1992
    ..46 mM. We conclude that dFdC-induced inhibition of dCMP deaminase resulted in a decrease of dFdCTP catabolism, contributing to the concentration-dependent elimination kinetics. This action constitutes a self-potentiation of dFdC activity...
  76. pmc Mechanisms of resistance to 5-aza-2'-deoxycytidine in human cancer cell lines
    Taichun Qin
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, USA
    Blood 113:659-67. 2009
    ..DAC induced DNA breaks as evidenced by H2AX phosphorylation and increased homologous recombination rates by 7- to 10-fold. These results suggest that in vitro resistance to DAC can be explained by insufficient incorporation into DNA...
  77. ncbi Expression of uracil DNA glycosylase (UDG) does not affect cellular sensitivity to thymidylate synthase (TS) inhibition
    S J Welsh
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Belmont, Surrey SM2 5NG, UK
    Eur J Cancer 39:378-87. 2003
    ....
  78. ncbi 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity
    Qian An
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
    Cancer Res 67:940-5. 2007
    ..The data provides a clearer understanding of the action of FU, suggesting predictive biomarkers of drug response and a mechanism for acquired resistance in tumors...
  79. ncbi [Late phase II study of S-1 in patients with advanced head and neck cancer]
    Y Inuyama
    Dept. of Otolaryngology, Hokkaido University School of Medicine
    Gan To Kagaku Ryoho 28:1381-90. 2001
    ..Therefore, this event was confirmed to be reversible. Based on these results, we conclude that S-1 is an active agent for the treatment of advanced/recurrent head and neck cancer...
  80. ncbi Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2',2'-difluorodeoxycytidine- induced cytotoxicity
    José García-Manteiga
    Departament de Bioquimica i Biologia Molecular Universitat de Barcelona, Barcelona, E 08071 Spain
    Clin Cancer Res 9:5000-8. 2003
    ..Indeed, it is not known which nucleoside transporters are expressed in human pancreas...
  81. pmc Gemcitabine-based chemogene therapy for pancreatic cancer using Ad-dCK::UMK GDEPT and TS/RR siRNA strategies
    Soukaina Rejiba
    Digestive Cancer Research Institute, Tumor Biology and Gene Therapy Department, IRCAD INSERM Unit 701, Strasbourg, France
    Neoplasia 11:637-50. 2009
    ..Together, these findings suggest that simultaneous TS/RRM2-gene silencing and dCK::UMK gene overexpression markedly improved gemcitabine's therapeutic activity. Clearly, this combined strategy warrants further investigation...
  82. ncbi Multiple-target chemotherapy (LV-modulated 5-FU bolus and continuous infusion, oxaliplatin, CPT- 11) in advanced 5-FU-refractory colorectal cancer: MTD definition and efficacy evaluation. A phase I-II study
    Andrea Bonetti
    Department of Oncology, Azienda Ospedaliera di Verona, Verona, Italy
    Tumori 92:389-95. 2006
    ....
  83. ncbi Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukaemia occurring during imatinib therapy
    K J Aichberger
    Medical University of Vienna, Austria
    Eur J Clin Invest 37:808-13. 2007
    ..The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain barrier...
  84. ncbi K-ras oncogene silencing strategy reduces tumor growth and enhances gemcitabine chemotherapy efficacy for pancreatic cancer treatment
    Soukaina Rejiba
    Institut de Recherche sur les Cancers de l Appareil Digestif IRCAD, INSERM Unit 701, Tumor Biology and Gene Therapy Department, Strasbourg 67091, France
    Cancer Sci 98:1128-36. 2007
    ..The improvement of gemcitabine-based chemotherapy suggests that this strategy might be used therapeutically against human pancreatic cancer to potentiate the effects of conventional therapy...
  85. ncbi A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer
    Y S Hong
    Department of Internal Medicine, Kangnam St Mary s Hospital, Seoul, Korea
    Ann Oncol 15:1344-7. 2004
    ..This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients...
  86. ncbi Gemcitabine: preclinical pharmacology and mechanisms of action
    W Plunkett
    Department of Clinical Investigation, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Semin Oncol 23:3-15. 1996
    ..Most importantly, the ratio of the cellular concentrations of gemcitabine triphosphate to deoxycytidine triphosphate increases, favoring analog incorporation into DNA, which is strongly associated with loss of viability...
  87. ncbi A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma
    Charles S Fuchs
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer 94:3186-91. 2002
    ..A recent trial reported a moderate antitumor activity for gemcitabine among Asian patients with advanced hepatocellular carcinoma. This led to our examination of the efficacy and tolerability of the drug in a population of U.S. patients...
  88. ncbi Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer
    E Villafranca
    Department of Oncology, Clinica Universitaria, University of Navarre, Pamplona, Spain
    J Clin Oncol 19:1779-86. 2001
    ..Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival...
  89. ncbi 5-fluorouracil derivatives induce differentiation mediated by tubulin and HLA class I modulation
    Juan A Marchal
    Departamento de Ciencias de la Salud, Universidade de Jaén, Jaen, Spain
    Med Chem 3:233-9. 2007
    ..These results could mean a more favorable prognosis of the patients affected with these tumors...
  90. ncbi Development of stealth liposome formulation of 2'-deoxyinosine as 5-fluorouracil modulator: in vitro and in vivo study
    Raphaelle Fanciullino
    Laboratoire de Pharmacocinetique, UFR Pharmacie, 27 Bd Jean Moulin, 13385, Marseille Cedex 05, France
    Pharm Res 22:2051-7. 2005
    ....
  91. ncbi Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells
    Kazuya Koizumi
    Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan
    Anticancer Res 25:3347-53. 2005
    ..In this study, we further investigated the implication of p38 MAPK in the cytotoxic action of gemcitabine...
  92. ncbi Antitumor activity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs
    Paola Brusa
    Dipartimento di Scienza e Tecnologia del Farmaco, Universita degli Studi di Torino, 10125 Torino, Italy
    Anticancer Res 27:195-9. 2007
    ..After intravenous injection, gemcitabine is rapidly converted to the inactive metabolite 2'-deoxy-2',2'-difluorouridine by cytidine deaminase...
  93. pmc Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas
    Tetsuhiko Shirasaka
    Kitasato Institute for Life Science, Kitasato University, Shirogane, Tokyo, Japan
    Jpn J Clin Oncol 39:2-15. 2009
    ..g. < or =Grade 1 anorexia, fatigue, stomatitis, nausea, vomiting and taste alteration). These two approaches are considered to allow long-lasting therapy with S-1...
  94. ncbi Adjuvant treatment of colorectal cancer at the turn of the century: European and US perspectives
    J Wils
    Oncology Unit, St Laurentius Hospital, Roermond, The Netherlands
    Ann Oncol 12:13-22. 2001
    ..As many clinical investigations have since been conducted in this setting, a comprehensive literature review was undertaken to clarify the role of adjuvant therapy in the treatment of colorectal cancer...
  95. ncbi Current status of epigenetic treatment in myelodysplastic syndromes
    Andrea Kuendgen
    Department of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University, Dusseldorf, Germany
    Ann Hematol 87:601-11. 2008
    ..The largest experience in MDS and acute myeloid leukemia exists with the anticonvulsant valproic acid. This review summarizes the existing clinical experience on HDACi and DNMT inhibitors...
  96. ncbi Cytotoxic chemotherapy for pancreatic cancer: Advances to date and future directions
    Henry Q Xiong
    The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Drugs 66:1059-72. 2006
    ..The search for effective therapy for advanced pancreatic cancer continues. Gemcitabine in combination with cytotoxic agents or molecular targeted agents hold promise...
  97. pmc Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy
    A M Gillespie
    Yorkshire Cancer Research Department of Clinical Oncology, Weston Park Hospital, Sheffield, UK
    Br J Cancer 82:1393-5. 2000
    ....
  98. ncbi Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer
    C H Kohne
    Department of Haematology Oncology and Tumor Immunology, Robert Rossle Klinik, Berlin, Germany
    J Clin Oncol 16:418-26. 1998
    ..To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer...
  99. ncbi Biliary tract cancer: our experience with gemcitabine treatment
    F Verderame
    Division of Internal Medicine, Service of Oncology, Azienda Ospedaliera Ospedali Civili Riuniti, Sciacca, AG, Italy
    Anticancer Drugs 11:707-8. 2000
    ....
  100. ncbi S-Phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine
    Z Shi
    Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences, Houston 77030, USA
    Cancer Res 61:1065-72. 2001
    ..These results differ from those in cells arrested at the G2 checkpoint, in which UCN-01 abrogates cell cycle arrest, permitting cells to progress in the cell cycle before apoptosis...
  101. ncbi Thymidylate synthase: a critical target for cancer chemotherapy
    Michal G Rose
    Department of Medicine, Yale Cancer Center, Yale University School of Medicine and VA CT Cancer Center, VA CT Healthcare System, New Haven, CT 06516, USA
    Clin Colorectal Cancer 1:220-9. 2002
    ..As the number of TS inhibitors available for general clinical use increases, further research is needed to elucidate the critical molecular and biochemical elements that determine the efficacy and tumor specificity of each compound...

Research Grants70

  1. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2003
    ..Ultimately, this work aims at establishing that methylation profiling may carry the same clinical implications as that already established for genetic profiling in neoplasia. ..
  2. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2008
    ..abstract_text> ..
  3. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2007
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. [unreadable] [unreadable]..
  4. Neoplasia and Methylated CpG Islands Amplification
    Jean Pierre Issa; Fiscal Year: 2004
    ..Ultimately, methylation profiling may prove very valuable in identifying subsets of patients with distinct clinical courses and response to specific therapeutic interventions, including using methylation inhibitors. ..
  5. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2004
    ....
  6. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2010
    ....
  7. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 2001
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  8. 2004 Conference on Advancing Cancer Care in Elderly
    WILLIAM ERSHLER; Fiscal Year: 2005
    ..ACCE will also feature the first annual "Giving Our Commitment to Survivorship Gala" in which the GOC will celebrate two cancer survivors who demonstrate unfailing optimism and advocacy while surviving cancer. ..
  9. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2007
    ..abstract_text> ..
  10. Clinical Significance of Apoptosis in Colon Cancer
    Frank Sinicrope; Fiscal Year: 2006
    ..abstract_text> ..
  11. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2003
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  12. MATH INTERVENTION FOR CHILDREN WITH LEUKEMIA
    Ida Moore; Fiscal Year: 2004
    ....
  13. Reversal of 5-FU Resistance by Arsenic Trioxide in Colorectal Carcinoma
    Bach Ardalan; Fiscal Year: 2008
    ..Aim 2: Determine if ATO administration down regulates the expression of thymidylate synthase in tumor and in PBMC in patients receiving ATO + 5-FU. [unreadable] [unreadable] [unreadable]..
  14. Aberrant Crypt Foci as a Biomarker for Chemoprevention
    Frank Sinicrope; Fiscal Year: 2009
    ....
  15. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2009
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  16. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2010
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  17. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2010
    ..abstract_text> ..
  18. Halogenated Alkenes and Microsomal GSH-transferases
    Michael J Kelner; Fiscal Year: 2010
    ..4] To determine the relative contribution of MGST1 and MGST2 to cellular antioxidant capacity through studies utilizing human MGST1 and MGST2 null cells. ..
  19. Changes in Tumor DNA Methylation with Decitabine
    David Stewart; Fiscal Year: 2006
    ..This preliminary look at individual genes may provide a molecular rationale for future decitabine therapeutic studies in specific relevant tumor types. ..
  20. Novel Method for Isolating Actively Translated mRNAs
    Jingfang Ju; Fiscal Year: 2007
    ..3.) Identify potential translationally regulated genes that are responsible for determining chemosensitivity during 5- fluorouracial (5-FU) treatment from human colon cancer samples. [unreadable] [unreadable] [unreadable]..
  21. CHONDROGENESIS AND HISTONE MODIFICATION ENZYMES
    Liu Yang; Fiscal Year: 2007
    ....
  22. Cytocidal Therapy In Vivo for Drug-Resistant Tumors
    Jason Koutcher; Fiscal Year: 2007
    ..If validated clinically, the proposed therapy will open the way for cure of metastatic breast cancer, and the therapeutic strategy likely will apply to other drug-resistant types of cancer. ..
  23. Effect of ethanol on retinoid metabolism and signaling in zebrafish embryos
    WILLIAM BOSRON; Fiscal Year: 2007
    ..We will assess the feasibility of performing targeted proteomics studies with tissues from other populations that express different SNPs in alcohol metabolizing enzymes. [unreadable] [unreadable] [unreadable]..
  24. The Environment and Epigenetic Gene Silencing in Cancer
    Stephen Baylin; Fiscal Year: 2009
    ..These, in turn, may be driven, and/or modulated, by key environmental factors. Thus, it is inferred that a key to cancer prevention may be to induce reversal of, or block, epigenetic gene silencing. ..
  25. Opposing Roles for MEK/ERK in Differentiation & Leukemia
    Daniel Johnson; Fiscal Year: 2009
    ....
  26. Rapid Screen for Genotoxicants, Chemoprotectors, and Radioprotectors
    Stephen Dertinger; Fiscal Year: 2008
    ..In addition, this assay can be used to investigate agents designed to ameliorate the effects of radiation exposure, e.g. biological response modifiers. [unreadable] [unreadable] [unreadable] [unreadable]..
  27. Development of a Perfusion-induced Systemic Hyperthermia Delivery Apparatus
    Joseph Zwischenberger; Fiscal Year: 2007
    ..The system is based on a Phase I clinical trial demonstrating the efficacy of such a treatment. [unreadable] [unreadable] [unreadable]..
  28. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna Shewach; Fiscal Year: 2007
    ..The results will aid us in optimizing current gene therapy protocols as well as initiate novel approaches for greater efficacy. ..
  29. Pharmacodynamics of Gemcitabine by MRS in Pancreatic CA
    Howard Hochster; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  30. The Role of XBP1 During Hypoxia and Tumor Growth
    Albert Koong; Fiscal Year: 2008
    ..Ultimately, these studies may not only lead to the development of novel anticancer therapies based upon inhibition of XBP1 in tumors, but may also provide fundamental insights into our understanding of tumorigenesis. ..
  31. Memorial Sloan Kettering Small Animal Imaging Research
    Jason Koutcher; Fiscal Year: 2006
    ..abstract_text> ..
  32. OPTIMIZING CANCER CHEMOTHERAPY
    Joan Bull; Fiscal Year: 2002
    ..Through such a hyperthermia-mediated multi- pronged attack, we hope to significantly increase the survival and quality of life of patients with common cancers. ..
  33. HEPATITIS C IN CHILDHOOD CANCER SURVIVORS
    Melissa Hudson; Fiscal Year: 2003
    ..abstract_text> ..
  34. CPT11 activation by carboxylesterases in colon cancer
    WILLIAM BOSRON; Fiscal Year: 2003
    ..If there is a positive correlation, a future multi-institutional study will be proposed. ..
  35. Cytokines in radiation lung injury
    ARTHUR BLACKSTOCK; Fiscal Year: 2003
    ..Even further, understanding the temporal expression of MIP-1alpha during thoracic radiation may allow the future utilization of anticytokine reagents, e.g. antibodies, receptor and synthesis blockers during treatment. ..
  36. FIBROBLAST CD 90 EXPRESSION IN FIBROGENIC SKIN DISORDERS
    James Hagood; Fiscal Year: 2002
    ..Establishing the role of fibroblast Thy-1/CD90 expression in human fibrogenic skin diseases is likely to unlock mechanisms of fibroblast activation and lead to more effective treatments for fibrotic disorders in skin and other tissues. ..
  37. TRIMODAL GENE THERAPY FOR PROSTATE CANCER
    SVEND FREYTAG; Fiscal Year: 2003
    ....
  38. RADIODIAGNOSIS & RADIOTHERAPY OF LUNG CANCER METASTASES
    AMIN KASSIS; Fiscal Year: 2004
    ....
  39. The Role of pRb in Hypoxia-mediated Cell Cycle Arrest
    NANCY KRUCHER; Fiscal Year: 2002
    ..The performance of the studies described in this proposal will serve as a basis to build upon in future studies directed toward increasing the efficacy of cancer treatment. ..
  40. Dermatomyositis Skin Disease Severity Measure Validation
    JOSPEH JORIZZO; Fiscal Year: 2003
    ..abstract_text> ..
  41. Retinoid Metabolism in Hepatitic Stellate Cells
    WILLIAM BOSRON; Fiscal Year: 2005
    ..Inhibitors of retinyl ester hydrolysis in stellate cells may be an effective therapeutic strategy for arresting stellate cell activation early in hepatic fibrosis. ..
  42. TLS and TLS Fusion Proteins in Leukemia
    Liu Yang; Fiscal Year: 2005
    ..It is envisioned that successful completion of this project will unveil potential therapeutic targets in the treatment of human leukemias characterized by the t(16;21) translocation. ..
  43. 500 MHz Wide Bore NMR System
    Jason Koutcher; Fiscal Year: 2002
    ..Thus this proposal, if funded , will support a very broad base of scientist and medical researchers in this area. ..
  44. CHEMOKINES/CYTOKINES AND RECEPTORS IN STEM CELL HOMING
    Hal Broxmeyer; Fiscal Year: 2005
    ..These studies should clarity the relevance of SDF-1 and CXCR4 for homing/engraftment and mobilization of primary stem/progenitor cells. ..
  45. Cell Cycle Controlling Genes in Adult Acute Lymphoma
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..abstract_text> ..
  46. GPX1 ENZYME REGULATION BY OXIDATIVE XENOBIOTICS
    Michael Kelner; Fiscal Year: 2002
    ..These studies will provide critical information regarding cellular response to oxidative stress and aid in determining if a common regulatory mechanism exists for GSH-dependent enzymes. ..
  47. Phase I trial of PHP with high-dose IL-2
    Wolfram Samlowski; Fiscal Year: 2006
    ..abstract_text> ..
  48. Dynamic Magnetic Resonance Imaging of Bone Tumors
    Jason Koutcher; Fiscal Year: 2007
    ..If successful, it will provide a tool to predict failure/response to chemotherapy, resulting in patient specific treatment which will likely enhance outcome. ..
  49. High Throughput Assay:Topoisomerase Enzyme Targets (RMI)
    JAMES STIVERS; Fiscal Year: 2005
    ..The utility of the assay has been validated, by screening a 2000 member small molecule library from which several novel lead compounds have been identified that specifically target a poxvirus family topoisomerase. ..
  50. Versatile Mutation Assay Platform
    Stephen Dertinger; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  51. Clinical application of multispectral imaging flow cytometry
    Hans Minderman; Fiscal Year: 2008
    ..The aim of the proposed studies is to determine necessary adjustments to this instrument's hardware and analysis software to accurately and efficiently use it in a clinical research setting. ..
  52. Imageable tumor-targeting bacteria
    Ming Zhao; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  53. DENDRITIC CELL THERAPY OF CHRONIC MYELOGENOUS LEUKEMIA
    Mark Litzow; Fiscal Year: 2003
    ..The combined data will provide a comprehensive understanding of the interaction of the immune system and CML and will yield information required for the rational design of more effective clinical protocols in the future. ..
  54. RHOMOCYCSTEINASE FOR HOMOCYSTEINE ASSAY
    Yuying Tan; Fiscal Year: 2002
    ..The tHCY enzymatic kits for these applications will be ready for commercial launch at this point. PROPOSED COMMERCIAL APPLICATION: Not Available ..
  55. Inhibitors of 5alpha-reductase for acne therapy
    Lingna Li; Fiscal Year: 2002
    ..PROPOSED COMMERCIAL APPLICATIONS: Liposomal 4-MA will be developed as a topical selectively targeted therapeutic for acne for which they should be a very market. ..
  56. FETAL GLOBIN INDUCTION IN BETA THALASSEMIA
    Susan Perrine; Fiscal Year: 2002
    ..These studies should determine the proportion and some genotypes of beta thalassemia patients which can benefit from Pulsed Butyrate plus/minus rhu-EP0 therapy. ..
  57. Adenoviral GFP targeting of metastatic human tumors using multiple delivery route
    Hiroyuki Kishimoto; Fiscal Year: 2008
    ..Having obtained these results, we can move forward in the Phase II grant application with experiments to bring OBP-401 to the clinic for use in cancer surgery in human patients. [unreadable] [unreadable] [unreadable]..
  58. Oral Therapeutic for Beta-Thalassemia
    Susan Perrine; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  59. Ethanol Effects on Antigen Presentation in Liver Cells
    Natalia Osna; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  60. Targeted tumoricidal bacteria
    Ming Zhao; Fiscal Year: 2007
    ..Future human trials of the tumor-killing bacteria can be held after the Phase I and Phase II grant periods are completed. [unreadable] [unreadable] [unreadable]..
  61. Erythropoiesis & pulse arginine butyrate in sickle cell
    Susan Perrine; Fiscal Year: 2005
    ..Abstract Not Provided ..
  62. Enzyme therapy for hyperhomocysteinemia
    Yuying Tan; Fiscal Year: 2005
    ..Phase II results will lead to an IND for MEGC-PEG-rMETase for end stage renal disease patients and other patients with intractable hyperhomocysteinemia and high cardiovascular disease mortality. ..
  63. Dual-color tumor-host imaging models
    Meng Yang; Fiscal Year: 2007
    ..These models have significant commercial potential for discovery and development of stroma-targeted and anti-angiogenesis drugs. [unreadable] [unreadable] [unreadable]..
  64. Therapeutic hair follicle-derived neurospheres
    Meng Yang; Fiscal Year: 2007
    ..Human hair- follicle bulge cells will be further characterized and developed for therapeutic potential for nerve regeneration in Phase III. [unreadable]..
  65. Pharmacophore-Modeled Screening for HbF-Inducing Agents
    Susan Perrine; Fiscal Year: 2004
    ..virtual screening using molecular modeling with confirmation by reporter assay and selection of a specific HDAC activity should generate additional compounds for development of an optimal HbF inducer for an effective life-long treatment ..
  66. Orthotopic models of tumor angiogenesis and blood flow
    Meng Yang; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  67. Discovery of novel fluorescent reporter genes
    Ming Zhao; Fiscal Year: 2004
    ..Reporters with spectral properties that can be used for whole-body imaging of tumors in the lung and their metastases will be candidates for further development for numerous applications of multi-color imaging. ..
  68. MOLECULAR BASIS FOR TS TRANSLATIONAL REGULATION
    Edward Chu; Fiscal Year: 2005
    ..Moreover, these molecular-based studies may provide the rational basis for the development of novel therapeutic strategies for human cancer. ..
  69. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  70. Molecular Regulation of Translational Regulation
    Edward Chu; Fiscal Year: 2008
    ..In this aim, we propose to identify the cellular mRNAs in addition to DHFR mRNA whose expression and/or function may be under the control of human DHFR protein. ..