Summary: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.

Top Publications

  1. ncbi Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
    Herbert Hurwitz
    Duke University, Durham, NC, USA
    N Engl J Med 350:2335-42. 2004
  2. ncbi Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer
    Eric Van Cutsem
    University Hospital Gasthuisberg, Digestive Oncology Unit, Herestraat 49, 3000 Leuven, Belgium
    N Engl J Med 360:1408-17. 2009
  3. ncbi Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen
    Eric Van Cutsem
    University Hospital Gasthuisberg, Leuven, Belgium
    J Clin Oncol 30:3499-506. 2012
  4. ncbi Topoisomerase I inhibitors: camptothecins and beyond
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
    Nat Rev Cancer 6:789-802. 2006
  5. ncbi A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer
    J Randolph Hecht
    David Geffen School of Medicine at UCLA, Santa Monica, CA 90404, USA
    J Clin Oncol 27:672-80. 2009
  6. ncbi DNA topoisomerases and their poisoning by anticancer and antibacterial drugs
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Chem Biol 17:421-33. 2010
  7. ncbi Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer
    Marc Peeters
    University Hospital Ghent, Ghent, Belgium
    J Clin Oncol 28:4706-13. 2010
  8. ncbi Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer
    David Cunningham
    Royal Marsden Hospital, London, United Kingdom
    N Engl J Med 351:337-45. 2004
  9. ncbi Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study
    E Van Cutsem
    University Hospital Gasthuisberg, Leuven, Belgium
    Ann Oncol 20:1842-7. 2009
  10. ncbi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009

Detail Information

Publications338 found, 100 shown here

  1. ncbi Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
    Herbert Hurwitz
    Duke University, Durham, NC, USA
    N Engl J Med 350:2335-42. 2004
    ..Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy...
  2. ncbi Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer
    Eric Van Cutsem
    University Hospital Gasthuisberg, Digestive Oncology Unit, Herestraat 49, 3000 Leuven, Belgium
    N Engl J Med 360:1408-17. 2009
  3. ncbi Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen
    Eric Van Cutsem
    University Hospital Gasthuisberg, Leuven, Belgium
    J Clin Oncol 30:3499-506. 2012
  4. ncbi Topoisomerase I inhibitors: camptothecins and beyond
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
    Nat Rev Cancer 6:789-802. 2006
    Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived...
  5. ncbi A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer
    J Randolph Hecht
    David Geffen School of Medicine at UCLA, Santa Monica, CA 90404, USA
    J Clin Oncol 27:672-80. 2009
    ..This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC...
  6. ncbi DNA topoisomerases and their poisoning by anticancer and antibacterial drugs
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Chem Biol 17:421-33. 2010
    ..We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes...
  7. ncbi Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer
    Marc Peeters
    University Hospital Ghent, Ghent, Belgium
    J Clin Oncol 28:4706-13. 2010
    ..This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status...
  8. ncbi Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer
    David Cunningham
    Royal Marsden Hospital, London, United Kingdom
    N Engl J Med 351:337-45. 2004
    ..We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan...
  9. ncbi Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study
    E Van Cutsem
    University Hospital Gasthuisberg, Leuven, Belgium
    Ann Oncol 20:1842-7. 2009
    ..The Bevacizumab Expanded Access Trial (BEAT) evaluated the safety and efficacy of bevacizumab plus first-line chemotherapy in a general cohort of patients with mCRC...
  10. ncbi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009
    ..We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies...
  11. ncbi Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nor
    Alfredo Falcone
    U O Oncologia Medica, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 25:1670-6. 2007
  12. pmc Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks
    Nasrollah Saleh-Gohari
    Institute for Cancer Studies, University of Sheffield Medical School, UK
    Mol Cell Biol 25:7158-69. 2005
    ..endonuclease or after stalling or collapsing replication forks following treatment with thymidine or camptothecin, respectively...
  13. ncbi PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
    Fotios Loupakis
    Department of Oncology, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 27:2622-9. 2009
    ..This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC)...
  14. ncbi Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05
    Valerie Boige
    Department of Medicine, Institut Gustave Roussy, Villejuif, France
    J Clin Oncol 28:2556-64. 2010
  15. pmc Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance
    Scott Kopetz
    University of Texas MD Anderson Cancer Center Lyndon B Johnson Hospital, Harris County Hospital District, Houston, TX, USA
    J Clin Oncol 28:453-9. 2010
  16. pmc UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy
    E Martinez-Balibrea
    Medical Oncology Service, Institut Catala d Oncologia, Hospital Germans Trias I Pujol C Ctra Canyet s n, Badalona 08916, Spain
    Br J Cancer 103:581-9. 2010
    ..Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU...
  17. pmc Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes
    R G Shao
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    EMBO J 18:1397-406. 1999
    ..In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated...
  18. ncbi Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Nature 434:108-13. 2005
    ..These data identify a defect in SSBR in a neurodegenerative disease, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons...
  19. pmc Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks
    Olivier Sordet
    Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892 4255, USA
    EMBO Rep 10:887-93. 2009
    ..We show the induction of DSBs and DDR activation in post-mitotic primary neurons and lymphocytes treated with camptothecin, with the induction of nuclear DDR foci containing activated ATM, gamma-H2AX (phosphorylated histone H2AX), ..
  20. ncbi Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial
    Gianluca Masi
    Unità Operativa Oncologia Medica Universitaria, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy
    Lancet Oncol 11:845-52. 2010
    ..We therefore assessed the safety and activity of the combination of FOLFOXIRI plus bevacizumab in patients with colorectal cancer...
  21. pmc Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741
    Hanna K Sanoff
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7305, USA
    J Clin Oncol 26:5721-7. 2008
  22. ncbi Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale
    Giuseppe Colucci
    Medical and Experimental Oncology Unit, Oncology Institute, Via Amendola 209, 70126 Bari, Italy
    J Clin Oncol 23:4866-75. 2005
    ..We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer...
  23. pmc Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I
    Nayun Kim
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Science 332:1561-4. 2011
    ..The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease...
  24. ncbi Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug
    G L Beretta
    Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
    Curr Med Chem 20:1541-65. 2013
    ..Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of ..
  25. ncbi Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial
    Gunnar Folprecht
    University Hospital Carl Gustav Carus, Medical Department I University Cancer Center, Dresden, Germany
    Lancet Oncol 11:38-47. 2010
    ..Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting...
  26. ncbi Effectiveness of liver metastasectomies in patients with metastatic colorectal cancer treated with FIr-B/FOx triplet chemotherapy plus bevacizumab
    Gemma Bruera
    Medical Oncology, S Salvatore Hospital, University of L Aquila, L Aquila, Italy
    Clin Colorectal Cancer 11:119-26. 2012
    ..The effectiveness of liver metastasectomies was evaluated in patients with MCRC who were treated with previously reported FIr-B/FOx (triplet chemotherapy plus bevacizumab)...
  27. ncbi Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activity
    Giovanni Capranico
    G Moruzzi Department of Biochemistry, University of Bologna, Bologna, Italy
    Biochim Biophys Acta 1806:240-50. 2010
    b>Camptothecin is a selective inhibitor of DNA topoisomerase I, and has effective antitumor activity...
  28. ncbi The price tag on progress--chemotherapy for colorectal cancer
    Deborah Schrag
    Memorial Sloan Kettering Cancer Center, New York, USA
    N Engl J Med 351:317-9. 2004
  29. ncbi Nanobiohybrids as delivery vehicles for camptothecin
    Katherine M Tyner
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
    J Control Release 95:501-14. 2004
    A novel method of delivering non-ionic, poorly water-soluble drugs such as campthothecin was developed. Camptothecin was first incorporated into micelles derived from negatively charged surfactants...
  30. ncbi Pharmacogenetics of irinotecan metabolism and transport: an update
    Nicola F Smith
    Molecular Pharmacology Section, Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA
    Toxicol In Vitro 20:163-75. 2006
    ..This report provides an update on current strategies to individualize irinotecan chemotherapy based on each patient's genetic constitution, which may ultimately lead to more selective use of this agent...
  31. pmc Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial
    C Garufi
    Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
    Br J Cancer 103:1542-7. 2010
  32. ncbi DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells
    C Arnaudeau
    Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Stockholm, S-106 91, Sweden
    J Mol Biol 307:1235-45. 2001
    ..In the present study, we investigated the molecular mechanism by which recombination resolves camptothecin (CPT)-induced DSB at DNA replication forks...
  33. pmc Systemic treatment of colorectal cancer
    Brian M Wolpin
    Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 134:1296-310. 2008
  34. ncbi Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer
    Hiroshi Nakagawa
    Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta 4259, Yokohama 226 8501, Japan
    Cancer Lett 234:81-9. 2006
    ..To circumvent the ABCG2-associated drug resistance, the structure-activity-relationship (SAR) of 14 new camptothecin (CPT) analogues has been studied with respect to the substrate specificity of ABCG2...
  35. ncbi FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study
    Christophe Tournigand
    Hopital Saint Antoine, 184 rue du Faubourg Saint Antoine, 75571 Paris, Cedex 12, France
    J Clin Oncol 22:229-37. 2004
    ..This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B)...
  36. pmc Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico
    Cinzia Tesauro
    Department of Biology and Interuniversity Consortium, National Institute Biostructures and Biosystems INBB, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome 00133 Italy
    Mol Cancer 12:100. 2013
    ..through different mechanisms, including clinically used drugs, such as the derivatives of the natural compound camptothecin that reversibly bind the covalent topoisomerase-DNA complex, slowing down the religation of the cleaved DNA ..
  37. pmc A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity
    Yeonee Seol
    Laboratory of Molecular Biophysics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:16125-30. 2012
    ..The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific ..
  38. pmc Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients
    Katerina Shulman
    CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
    Cancer 117:3156-62. 2011
    ..The UGT1A1 gene encodes for an enzyme that metabolizes irinotecan, and its genetic variants were shown to be associated with increased drug toxicity. We evaluated clinical outcomes associated with the UGT1A1*28 variant...
  39. ncbi Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer
    Masahide Ikeguchi
    Department of Surgery, Division of Surgical Oncology, School of Medicine, Tottori University, 36 1 Nishi cho, Yonago, 683 8504, Japan
    Surg Today 41:1196-9. 2011
    ..This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC...
  40. ncbi The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells
    G M Rath
    Universite de Reims Champagne Ardenne, IFR 53 Biomolecules, UMR CNRS 6198 Matrice Extracellulaire et Régulation Cellulaire, UFR Sciences de Reims, Moulin de la Housse BP 1039 51687 Reims Cedex 2, France
    Biochim Biophys Acta 1763:1125-34. 2006
    b>Camptothecin and doxorubicin belong to a family of anticancer drugs that exert cytotoxic effects by triggering apoptosis in various cell types...
  41. ncbi Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways
    Cheng Wu Zeng
    Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat Sen University, Guangzhou, China
    Mol Pharmacol 81:578-86. 2012
    b>Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood...
  42. pmc Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks
    Claudia Kerzendorfer
    Human DNA Damage Response Disorders Group, University of Sussex, Brighton, UK
    Hum Mol Genet 19:1324-34. 2010
    ..We show that these patient-derived cells exhibit sensitivity to camptothecin (CPT), impaired CPT-induced topoisomerase I (Topo I) degradation and ubiquitination, thereby suggesting Topo I ..
  43. pmc Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial
    Janja Ocvirk
    Institute of Oncology, 1000 Ljubljana, Slovenia
    World J Gastroenterol 16:3133-43. 2010
    ..To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC)...
  44. ncbi Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy
    A Ruzzo
    Institute of Biochemistry G Fornaini, University of Urbino, Urbino, Italy
    Pharmacogenomics J 8:278-88. 2008
    ..Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies...
  45. pmc Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M
    Thiyam Ramsing Singh
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Blood 114:174-80. 2009
    ..FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light...
  46. ncbi The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer
    Giuseppe Toffoli
    Experimental and Clinical Pharmacology Unit, Medical Oncology unit of Centro di Riferimento Oncologico, National Cancer Institute, Via Pedemontana Occidentale, 12, 33081, Aviano, Italy
    J Clin Oncol 24:3061-8. 2006
    ..UGT1A1*28 polymorphism has been associated with decreased glucuronidation of SN38, the active metabolite of irinotecan. This could increase toxicity with this agent...
  47. ncbi Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin
    Ji Youn Han
    Research Institute and Hospital, National Cancer Center, Goyang, Korea
    J Clin Oncol 24:2237-44. 2006
    ..To determine whether uridine diphosphate-glucuronosyltransferase 1A1, UGT1A7, and UGT1A9 polymorphisms affect the pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non-small-cell lung cancer (NSCLC)...
  48. ncbi UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity
    L Iyer
    Department of Medicine, The University of Chicago, IL, USA
    Pharmacogenomics J 2:43-7. 2002
    ..The results suggest that screening for UGT1A1*28 polymorphism may identify patients with lower SN-38 glucuronidation rates and greater susceptibility to irinotecan induced gastrointestinal and bone marrow toxicity...
  49. doi Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study
    Charles S Fuchs
    J Clin Oncol 26:689-90. 2008
  50. ncbi Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis
    Gianluca Masi
    U O Oncologia Medica 2 Universitaria Polo Oncologico, Azienda Ospedaliero Universitaria Pisana, Via Roma, 67 56126 Pisa, Italy
    J Natl Cancer Inst 103:21-30. 2011
  51. ncbi Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3
    Eric Van Cutsem
    Digestive Oncology Unit, University Hospital Gasthuisberg Leuven, Herestraat 49, 3000 Leuven, Belgium
    J Clin Oncol 27:3117-25. 2009
    ..CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone...
  52. ncbi Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex
    Bart L Staker
    deCODE BioStructures, 7869 NE Day Road West, Bainbridge Island, Washington 98110, USA
    J Med Chem 48:2336-45. 2005
    ..Science 1998, 729, 1534-1541.) We report the X-ray crystal structures of the human top1-DNA complex bound with camptothecin and representative members of the indenoisoquinoline and indolocarbazole classes of top1 poisons...
  53. ncbi Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases
    Gianluca Masi
    Unità Operativa Oncologia Medica, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    Ann Surg 249:420-5. 2009
    ..The objective of this study was to evaluate the long-term outcome of resected patients and the impact of FOLFOXIRI on perioperative morbidities, mortality, and chemotherapy induced hepatotoxicity...
  54. pmc A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability
    Brenda C O'Connell
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 40:645-57. 2010
    Replication stress involving collision of replisomes with camptothecin (CPT)-stabilized DNA-Topoisomerase I adducts activates an ATR-dependent pathway to promote repair by homologous recombination...
  55. pmc Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803
    Monica M Bertagnolli
    Brigham and Women s Hospital, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Clin Oncol 27:1814-21. 2009
    ..This prospective study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient (MMR-D) colon cancers...
  56. pmc Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer
    B Glimelius
    Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
    Pharmacogenomics J 11:61-71. 2011
    ..Carriers of the ABCB1 1236T-2677T-3435T haplotype responded to treatment less frequently (43 vs 67%, P=0.027), and survived shorter time, OR=1.56 (95% CI=1.01-2.45)...
  57. pmc Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models
    Cynthia X Ma
    Section of Breast Oncology, Division of Oncology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    J Clin Invest 122:1541-52. 2012
    ..In addition, knockdown of p53 sensitized WU-BC3 tumors to the combination therapy. These results demonstrate that p53 is a major determinant of how TNBCs respond to therapies that combine DNA damage with Chk1 inhibition...
  58. ncbi Impact of the UGT1A1*28 allele on response to irinotecan: a systematic review and meta-analysis
    Mafalda M Dias
    University of South Australia, Division of Health Sciences, School of Pharmacy and Medical Sciences, GPO Box 2471, Adelaide, South Australia 5001, Australia
    Pharmacogenomics 13:889-99. 2012
    ..Whether UGT1A1*28 genotype is associated with irinotecan response therefore is an important gap in existing knowledge to inform clinical utility...
  59. ncbi Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab
    Bart Jacobs
    Department of Pathology, Digestive Oncology Unit, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
    J Clin Oncol 27:5068-74. 2009
  60. pmc CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA binding, and increases cellular camptothecin sensitivity
    Keya Bandyopadhyay
    Torrey Pines Institute for Molecular Studies, San Diego, California, United States of America
    PLoS ONE 7:e50427. 2012
    Topoisomerase I is the target for a potent class of chemotherapeutic drugs derived from the plant alkaloid camptothecin that includes irinotecan and topotecan...
  61. ncbi A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer
    Iben Kümler
    Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark
    Breast Cancer Res Treat 138:347-58. 2013
    ..However, a large proportion of patients do not respond, thus emphasizing the need for a biomarker predictive of response to irinotecan in order to introduce this drug as the standard treatment for MBC...
  62. ncbi Phase 2 study of capecitabine and irinotecan combination chemotherapy (modified XELIRI regimen) in patients with advanced gastric cancer
    Hui Yan Luo
    Department of Medical Oncology, Sun Yat sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Guangzhou, People s Republic of China
    Am J Clin Oncol 34:555-60. 2011
    ..A phase 2 trial was conducted to determine the efficacy and tolerability of the modified combination regimen of capecitabine and irinotecan (mXELIRI) in patients with AGC...
  63. pmc Exploring DNA topoisomerase I ligand space in search of novel anticancer agents
    Malgorzata N Drwal
    Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia
    PLoS ONE 6:e25150. 2011
    ..Pharmacophore models have been developed based on the molecular characteristics of derivatives of the alkaloid camptothecin (CPT), which represent potent antitumour agents and the main group of Top1 inhibitors...
  64. ncbi Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles
    Cheng Liang Peng
    Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No 1, Section 1, Jen Ai Road, Taipei 100, Taiwan
    Biomaterials 30:3614-25. 2009
    ..Therefore, this SN-38/CBSC delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer...
  65. ncbi Dynamic proteomics of individual cancer cells in response to a drug
    A A Cohen
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Science 322:1511-6. 2008
    ..we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different ..
  66. pmc Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants
    Supaart Sirikantaramas
    Graduate School of Pharmaceutical Sciences, Chiba University, 1 33 Yayoi cho, Inage Ku, Chiba 263 8522, Japan
    Proc Natl Acad Sci U S A 105:6782-6. 2008
    ..The plant-derived anticancer alkaloid camptothecin (CPT) induces cell death by targeting DNA topoisomerase I (Top1), the enzyme that catalyzes changes in DNA ..
  67. ncbi Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer
    Ji Youn Han
    Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
    Lung Cancer 63:115-20. 2009
    ..3, 5.6, and 5.1, respectively). Patient selection based on integrated pharmacogenetic model would be helpful for predicting irinotecan-PK and severe toxicities in NSCLC patients...
  68. pmc Early clinical development of ARQ 197, a selective, non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers
    Alex A Adjei
    Roswell Park Cancer Institute, Buffalo, New York, USA
    Oncologist 16:788-99. 2011
  69. ncbi Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery
    L Rubbia-Brandt
    Unit of Gastrointestinal and Liver Pathology, University Hospital, Geneva, Switzerland
    Ann Oncol 18:299-304. 2007
  70. ncbi Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan
    Karen Lise Garm Spindler
    Departments of Oncology and Biochemistry, Vejle Hospital, Vejle Department of Radiation Oncology, Rigshospitalet, Copenhagen, Denmark
    Clin Cancer Res 18:1177-85. 2012
  71. pmc Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124
    Primo N Lara
    University of California Davis Cancer Center, Sacramento, CA 95817, USA
    J Clin Oncol 27:2530-5. 2009
    ..To confirm those results and discern the potential role of population-related pharmacogenomics (PG) in outcomes, we conducted a large randomized trial of identical design to the Japanese trial in North American patients with E-SCLC...
  72. ncbi Ratiometric dosing of anticancer drug combinations: controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice
    Lawrence D Mayer
    Celator Pharmaceuticals Corp, 1779 West 75th Avenue, Vancouver, BC, Canada V6P 6P2
    Mol Cancer Ther 5:1854-63. 2006
  73. pmc Phase III noninferiority trial comparing irinotecan with oxaliplatin, fluorouracil, and leucovorin in patients with advanced colorectal carcinoma previously treated with fluorouracil: N9841
    George P Kim
    Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    J Clin Oncol 27:2848-54. 2009
    ..Cross-over to the other treatment on disease progression was mandated...
  74. ncbi Antibody targeting of camptothecin-loaded PLGA nanoparticles to tumor cells
    Paul A McCarron
    School of Pharmacy, Queen s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, U K
    Bioconjug Chem 19:1561-9. 2008
    ..the Fas receptor (CD95/Apo-1) covalently attached to poly(lactide-co-glycolide) nanoparticles (NP) loaded with camptothecin. Variations in surface carboxyl density permitted up to 48...
  75. ncbi Mechanism of action of camptothecin
    L F Liu
    Department of Pharmacology, UMDNJ Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
    Ann N Y Acad Sci 922:1-10. 2000
    b>Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I)...
  76. pmc Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines
    Therese Bredholt
    The Gade Institute, University of Bergen, Bergen, Norway
    Mol Cancer 8:101. 2009
    ..triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid ..
  77. ncbi Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases
    Dan G Blazer
    Department of Surgical Oncology, Gastrointestinal Medical Oncology, and Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 4009, USA
    J Clin Oncol 26:5344-51. 2008
    ..The secondary goal of the study was to identify the clinical predictors of pathologic response...
  78. pmc Cancer therapies utilizing the camptothecins: a review of the in vivo literature
    Vincent J Venditto
    Department of Chemistry, Texas A and M University, College Station, Texas 77843, USA
    Mol Pharm 7:307-49. 2010
    ..summarizes the in vivo assessment-preliminary, preclinical, and clinical-of chemotherapeutics derived from camptothecin or a derivative...
  79. ncbi Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats
    Andrea M Stringer
    Department of Medical Oncology, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia
    Cancer Biol Ther 7:1919-25. 2008
    ..However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to be involved...
  80. pmc The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress
    You Wei Zhang
    Department of Pharmacology, Case Comprehensive Caner Center, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Wood Building W343A, Cleveland, OH 44106, USA
    Mol Cell 35:442-53. 2009
    ..stress-induced Chk1 degradation are associated with cancer cell resistance to the chemotherapeutic agent, camptothecin. We propose that Fbx6-dependent Chk1 degradation contributes to S phase checkpoint termination and that a ..
  81. ncbi Effect of a novel vacuolar-H+-ATPase inhibitor on cell and tumor response to camptothecins
    Giovanna Petrangolini
    Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy
    J Pharmacol Exp Ther 318:939-46. 2006
    ..Such findings support a potential interest for the use of vacuolar-H(+)-ATPase inhibitors in combination therapy to improve camptothecin efficacy.
  82. ncbi Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo
    Deshan Yu
    Enzon Pharmaceuticals, Inc, Piscataway, NJ 08854, USA
    J Control Release 110:90-102. 2005
    Antitumor effect of poly(ethylene glycol)-camptothecin conjugate (PEG-CPT) was studied in the nude mouse model of human colon cancer xenografts...
  83. pmc Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma
    Nancy E Kemeny
    Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, 1275 York Ave, New York, NY 10065, USA
    J Clin Oncol 27:3465-71. 2009
    ..Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability...
  84. ncbi Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: tumor-tropic potential and inhibition of ovarian cancer cell growth
    Ki Yon Kim
    Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Cancer Sci 101:955-62. 2010
    ..derived from the ascites of an ovarian cancer patient) with the prodrugs 5-fluorocytosine (5-FC) or camptothecin-11 (CPT-11) in the presence of HB1.F3.CD or HB1.F3...
  85. pmc WRN helicase regulates the ATR-CHK1-induced S-phase checkpoint pathway in response to topoisomerase-I-DNA covalent complexes
    Birija Sankar Patro
    Department of Molecular Biology, University of Aarhus, C F Mollers Allé 3, DK 8000 Aarhus C, Denmark
    J Cell Sci 124:3967-79. 2011
    ..Together, our results strongly suggest an essential regulatory role for WRN in controlling the ATR-CHK1-mediated S-phase checkpoint in CPT-treated cells...
  86. ncbi Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest
    Aime A Levesque
    Department of Pharmacology and Toxicology and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Mol Cancer Ther 7:252-62. 2008
  87. pmc A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells
    Ning Wu
    Institute of Medicinal Chemistry, Sun Yat Sen University, Guangzhou 510006, China
    Biochemistry 49:10131-6. 2010
    ..Our present results indicate that CY13II shows more potent antiproliferative activity against K562 cells than camptothecin. Additionally, K562 cells were arrested in G2/M, and their growth rate decreased after treatment with CY13II at ..
  88. pmc Protein kinase CK2 is a central regulator of topoisomerase I hyperphosphorylation and camptothecin sensitivity in cancer cell lines
    Keya Bandyopadhyay
    Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, United States
    Biochemistry 50:704-14. 2011
    Topoisomerase I (topo I) is required to unwind DNA during synthesis and provides the unique target for camptothecin-derived chemotherapeutic agents, including Irinotecan and Topotecan...
  89. pmc New Topoisomerase I mutations are associated with resistance to camptothecin
    Celine Gongora
    Institut de Recherche en Cancérologie de Montpellier, INSERM, Université Montpellier1, CRLC Val d Aurelle Paul Lamarque, Montpellier, France
    Mol Cancer 10:64. 2011
    ..TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecan's active metabolite)...
  90. ncbi Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases
    Felix G Fernandez
    Section of Hepatobiliary Pancreatic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Coll Surg 200:845-53. 2005
    ..The objective was to evaluate the effect of preoperative administration of newer chemotherapeutic agents (irinotecan and oxaliplatin) on development of steatohepatitis, which could limit surgical options...
  91. ncbi Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model
    Puja Sapra
    Enzon Pharmaceuticals, Inc, Piscataway, New Jersey 08854, USA
    Clin Cancer Res 14:1888-96. 2008
    Clinical development of SN38, the active metabolite of camptothecin-11 (CPT-11), has been hampered due to its poor solubility...
  92. ncbi Clinical and pharmacogenetic factors associated with irinotecan toxicity
    Dinemarie Kweekel
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Cancer Treat Rev 34:656-69. 2008
    ..Future studies should combine pharmacogenetics with clinical determinants such as performance status and co-medication as to predict irinotecan toxicity and to develop predefined dosing algorithms...
  93. ncbi Preoperative chemotherapy does not increase morbidity or mortality of hepatic resection for colorectal cancer metastases
    Charles R Scoggins
    Division of Surgical Oncology, James Graham Brown Cancer Center, University of Louisville, 315 E Broadway, Suite 303, Louisville, KY 40202, USA
    Ann Surg Oncol 16:35-41. 2009
    ..Pre-hepatectomy chemotherapy appears to be safe and is an important part of the multidisciplinary approach for this disease...
  94. pmc Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells
    Yong Wei Zhang
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA
    Nucleic Acids Res 39:3607-20. 2011
    ..The present study explores the molecular rationale for combining veliparib (ABT-888) with camptothecin (CPT) and its clinical derivatives, topotecan and irinotecan...
  95. ncbi Prognostic role of serum vascular endothelial growth factor, basic fibroblast growth factor and nitric oxide in patients with colorectal carcinoma
    Hakan Akbulut
    Department of Medical Oncology, Ibni Sina Hospital, Ankara University Faculty of Medicine, Sihhiye, Ankara 06100, Turkey
    Cytokine 20:184-90. 2002
    ..032, Cox regression analysis). In conclusion, serum VEGF and NO levels have prognostic role in patients with CRC and the new angiogenesis index using the serum levels of the factors seem to be useful...
  96. ncbi Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104--a randomized trial of the German AIO CRC study group
    Nicolas Moosmann
    University of Munich, Klinikum Muenchen Grosshadern, Germany
    J Clin Oncol 29:1050-8. 2011
  97. ncbi Hepatic intra-arterial injection of drug-eluting bead, irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study
    Robert C G Martin
    Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA
    Ann Surg Oncol 18:192-8. 2011
    ..The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy...
  98. pmc Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy
    V Catalano
    Medical Oncology, Azienda Ospedaliera Ospedale San Salvatore, Pesaro, Italy
    Br J Cancer 100:881-7. 2009
  99. ncbi Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American
    Nahoko Kaniwa
    Division of Medicinal Safety Science, National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya Ku, Tokyo 158 8501, Japan
    Drug Metab Dispos 33:458-65. 2005
    ..The variation 686C>T may cause high toxicity during 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) therapy or hyperbilirubinemia in patients...
  100. pmc Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study
    Astrid Lievre
    Gastroenterology and Digestive Oncology Unit, Assistance Publique Hopitaux de Paris, Hopital Ambroise Pare, Boulogne Billancourt, France
    BMC Cancer 9:347. 2009
    ..The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin...
  101. pmc Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer
    Kae Hashimoto
    Toronto, ON M4N 3M5, Canada
    Mol Cancer Ther 9:996-1006. 2010
    ..Mol Cancer Ther; 9(4); 996-1006. (c)2010 AACR...

Research Grants64

  1. p53 Acetylation as a Mechanism in Chemoprevention by Aspirin
    JAYARAMA B GUNAJE; Fiscal Year: 2010
    ..Interestingly, in DNA damaged cells (induced by camptothecin), aspirin treatment (24 h) inhibited the p21 induction, while the Bax induction was unaffected...
  2. Discovery Tools for Chemotherapy Resistance to Cell Death.
    Robert W Sobol; Fiscal Year: 2012
    ..multiple apoptotic and autophagy endpoints and selective response to apoptosis inducing agents (Temozolomide, Camptothecin, staurosporine and Sulindac)...
  3. Novel Topoisomerase I Inhibitors
    MARK S CUSHMAN; Fiscal Year: 2013
    ..of synthetic methods will be employed in the syntheses of new Top I inhibitors, including indenoisoquinoline-camptothecin hybrids termed "aromathecins", nitrogen analogues of the aromathecins, and azaindenoisoquinolines...
  4. Ras18-mediated Fanconi Anemia pathway activation in response to camptothecin
    Komaraiah Palle; Fiscal Year: 2013
    ..mechanisms that repair DNA damage induced by DNA topoisomerase I (Top1) -targeting anticancer drugs such as camptothecin (CPT) and its analogues...
  5. Analysis of replication fork-collapse in yeast by site-specific DNA nicking
    RANJITH PRASAD ANAND; Fiscal Year: 2013
    ..have a free 5'end but protein-attached 3'end and resemble the lesion created by the antitumor drug camptothecin's inhibition of Topoisomerase I...
  6. Synthesis, Biosynthesis, and Structure of Antitumor Agents
    Thomas R Hoye; Fiscal Year: 2013
    ..from daunomycin), etoposide/teniposide (from podophyllotoxin), irinotecan/topotecan (from camptothecin), mitomycin, mylotarg (from calicheamicin), streptozotocin, taxol (and docetaxel), vincristine, and vinblastine...
  7. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    ..that Rad18 colocalizes with DNA double strand breaks (DSBs) when cells are exposed to ionizing radiation, camptothecin, Mitomycin C, or cisplatin and that depletion of Rev3 leads to cellular phenotypes consistent with cells ..
  8. Multifunctional PEG Hydrogel Nano/Microparticles for Targeted Treatment of NSCLC
    Patrick J Sinko; Fiscal Year: 2013
    ..AIM 2: Design, fabricate, and assess NPs and GMPs that enhance the pro-apoptotic effect of camptothecin (CPT)...
  9. Spatiotemporal Regulation of Chk1 in Cell Biology, Cancer Etiology and Therapy
    You Wei Zhang; Fiscal Year: 2013
    ..of active Chk1 proteins leads to the resistance of cancer cells to a clinically used chemotherapeutic drug, camptothecin (CPT). This is probably because Chk1-profient cells are better equipped to handle DNA damage induced by CPT...
  10. Understanding the Mechanistic Roles of Mec1-dependent Phosphorylation in Replicat
    Patrice Y Ohouo; Fiscal Year: 2012
    ..generated here will help understand how cells can survive in the presence of fork damaging agents such as camptothecin analogues, cisplatin and hydroxyurea, which are commonly used in cancer treatment...
  11. Regulation and Function of the p14ARF/topoisomerase I Complex in Cancer
    Ruth A Gjerset; Fiscal Year: 2012 to develop improved ways to suppress cancer through modulation of topoisomerase I, an important target for camptothecin-like chemotherapeutic drugs, and to further elucidate how the p14ARF/topoisomerase I complex contributes to the ..
  12. Tumorigenic Role of the CUL4A Ubiquitin Ligase
    Pengbo Zhou; Fiscal Year: 2013
    ..the specific ubiquitin-proteolytic events that underlie tumor initiation, maintenance, and resistance to camptothecin-type chemotherapy drugs...
  13. Macromolecular therapeutics for neoplastic meningitis
    Mikhail I Papisov; Fiscal Year: 2011
    ..macromolecules labeled with iodine-124, investigate by PET their retention in CSF, then synthesize a camptothecin conjugate of the optimal size with respect to CSF retention, investigate by PET how the conjugate distributes ..
  14. Nanomicellar Formulation for Synergistic Targeting of Prostate Cancer
    Song Li; Fiscal Year: 2013
    ..importantly, PEG-embelin becomes a highly efficient solubilizing agent for other compounds including PTX and camptothecin. We hypothesize that PEG-embelin conjugates can serve as a safe and dual functional carrier system to achieve ..
  15. Selective Inhibitors to Improve CPT-11 Therapy
    Philip M Potter; Fiscal Year: 2013
    Abstract CPT-11 is a highly effective, camptothecin-based anticancer agent that is currently approved for the treatment of colon cancer...
  16. Layer-by-layer nanocarriers for highly efficient solubilization of insoluble drug
    Vladimir P Torchilin; Fiscal Year: 2013
    ..the following specific aims: (1) To prepare stable nanocolloids of poorly soluble drugs - paclitaxel (PCT), and camptothecin (CPT) - with a size of 100-to-200 nm, drug content of above 75% wt, and controllable drug release rate by using ..
  17. Biodegradable Drug-Eluting Surgical Meshes with Tunable Release Kinetics
    JOHN JOHN SCHWARTZ; Fiscal Year: 2013
    ..elimination of burst release kinetics to guard against acute toxicity, 3) maintenance of stable lactone form of camptothecin drug, 4) full biodegradation over 3-6 months to avoid a chronic foreign body response, and 5) demonstration of ..
  18. Camptothecin-Containing Nanoparticles: Control Over Particle Size, Biodistributio
    Jianjun Cheng; Fiscal Year: 2012
    ..We also aim to develop camptothecin-containing, monodisperse, fast-degrading silica NPs with the size and surface property optimized based on ..
  19. Topoisomerase 1 and mutagenesis in yeast
    Sue Jinks-Robertson; Fiscal Year: 2013
    ..Aim 4 will define factors that trap the Top1cc during transcription and will explore the mutagenic potential of camptothecin, a chemotherapeutic drug that stabilizes the Top1cc...
  20. Identification and targeting of colon cancer initiating cells
    Natasha Y Frank; Fiscal Year: 2013
    ..For example, inhibition of ABCB5 renders normally resistant melanoma cells susceptible to doxorubicin, camptothecin and 5-FU...
  21. Camptothecin Analogs for Cancer Therapy
    Lee Roy Morgan; Fiscal Year: 2011
    ..applicant): 7-Butyl-10-aminocamptothecin (BACPT), as a water-soluble dipeptide pro-drug - BACPTDP, is a novel camptothecin analog that has increased activity in hypoxic/acidic tumor tissues, characteristic of fast growing cancers that ..
  22. Biocompatible Dendritic Polymers for in vivo Applications
    FRANCIS SZOKA; Fiscal Year: 2009
    ..that the optimal release rate will differ for each anticancer agent tested: doxorubicin, cis-platinum, a camptothecin derivative, a fluoropyrimidine and paclitaxel...
  23. Nanovalve Platform: Targeted, Controlled, Release of Anticancer Drugs
    Jeffrey I Zink; Fiscal Year: 2013
    ..DNA binding agent and to demonstrate the delivery and on-demand release of anticancer drugs (paclitaxel, camptothecin and doxorubicin) in human carcinoma cell lines...
  24. Optimization of dipeptide-linked benzimidazole topoisomerase 1 poisons
    Craig Beeson; Fiscal Year: 2009
    Derivatives of camptothecin (CPT) that inhibit Topoisomerase I (Top1) activity have demonstrated clinical utility in the treatment of various cancers...
  25. Drug Delivery Systems Based on Cleavable Oxanorbornadienes
    ALEXANDER KISLUKHIN; Fiscal Year: 2012
    ..In a proof-of-concept study, a highly active but poorly soluble camptothecin derivative known as SN-38 will be employed...
    Vladimir Torchilin; Fiscal Year: 2007
    ..diacyllipid-based micelles loaded with poorly soluble anticancer drugs, such as taxol, camptothecin, and porphyrin derivatives (M-porphyrin), will provide an increased anticancer effect both in vitro and in vivo,..
  27. Anti-Cancer Drug Design Targeting Human Topoisomerase I
    Lance Stewart; Fiscal Year: 2002
    Human topoisomerase I (topo I) is the sole intracellular target of camptothecin (CPT) and other "topo I poisons," some of which are among the most promising anticancer drugs ever identified. Emerald BioStructures, Inc...
    YUE WEI LEE; Fiscal Year: 2001
    ..inhibitory activity against the DNA topoisomerase I enzyme: It is 3 times more potent than the standard, camptothecin, in the topoisomerase I relaxation assay...
  29. A novel diagnostic test for Irinotecan and Topotecan sensitivity
    Ruth A Gjerset; Fiscal Year: 2013
    ..diagnostic assay to detect tumor responsiveness to a widely used class of chemotherapeutic agents derived from camptothecin that includes Irinotecan and Topotecan...
    Angeline Douvas; Fiscal Year: 1990
    ..Conversely, the effects of the topo I inhibitor camptothecin on procollagen mRNA levels will be investigated by dot blot hybridization...
  31. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
    ..b>Camptothecin (CPT) was the first TOP1 poison identified...
    Ian McLennan; Fiscal Year: 2002
    ..The hybrid nanospheres will be used to encapsulate several different antineoplastic agents including camptothecin derivatives and BCNU. The starch hybrids will be cast as thin films with the incorporated drug...
    Erasmus Schneider; Fiscal Year: 2001
    ..MCF7, MCF7/MX, that has been selected for mitoxantrone resistance, exhibits unusual cross-resistance to several camptothecin analogs such as topotecan and irinotecan...
  34. Improved Use of Camptothecins for Small Cell Lung Cancer
    John Murren; Fiscal Year: 2004
    ..To understand better the mechanisms involved in camptothecin cytotoxicity, we established and characterized several camptothecin resistant and partially revertant human ..
    ROBERT SNAPKA; Fiscal Year: 2002
    ..The hypothesis of this proposed study is that our understanding of the molecular biology of camptothecin action can be significantly advanced by two developments of the SV40 model system: (1) the study of ..
    OLIVER COLVIN; Fiscal Year: 2000
    ..more potent and selective inhibitors of topoisomerase I will be synthesized, based upon recent success with camptothecin (CPT) analogs that act as water-soluble prodrugs...
    Daniel Fernandes; Fiscal Year: 2003
    ..Specific Aims 2b and 2c are designed to assess some of the cellular responses to VM-26 and camptothecin induced damage to matrix-attached DNA loops...
    Eric Rubin; Fiscal Year: 1999
    ..Knowledge of factors involved in the interaction between the enzyme and inhibitors such as camptothecin would be of benefit in the clinical application of these agents...
    George Stark; Fiscal Year: 1999
    ..of DNA synthesis (using N-(phosphonacetyl)-L-aspartate (PALA) or aphidicolin) or DNA damage (using adriamycin, camptothecin or radiation)...
    John Murren; Fiscal Year: 2000
    ..Irinotecan is a camptothecin derivative with significant activity in NSCLC...
    Nathan Berger; Fiscal Year: 2000
    ..Microenzymatic assays of topoisomerase I and Il activities and susceptibility to camptothecin analogs will be performed on CT- or bronchoscopic-guided biopsy specimens obtained from tumors of patients ..
    Lance Stewart; Fiscal Year: 2000
    Human topoisomerase I (topoI) is the sole intracellular target of camptothecin (CPT) and other "topo I poisons," some of which are among the most promising anticancer drugs ever identified. Emerald BioStructures, Inc...
    Ya Wang; Fiscal Year: 2002
    DESCRIPTION: Camptothecin (CPT) and its analogs are topoisomerase I (Topo I) inhibitors and show efficacy against solid tumors which have been historically resistant to most cancer chemotherapeutic agents...
  44. Aerosol Therapy for Lung Cancer
    Brian Hansen; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
    Danzhou Yang; Fiscal Year: 2004
    ..grant application is to explore the molecular level details of the DNA and topoisornerase I interactions of the camptothecin family of anticancer drugs...
    Mary Ann Bjornsti; Fiscal Year: 2003
    ..As exemplified by camptothecin (Cpt), these drugs target Top1 by increasing the stability of the covalent enzyme-DNA intermediate...
  47. Potent Topoisomerase I Inhibition For Glioma Therapy
    Thomas Burke; Fiscal Year: 2001 silatecan (silylcamptothecin) analog that displays superior blood stability relative to the FDA-approved camptothecin congeners, topotecan and CPT- 11...
    Eric Rubin; Fiscal Year: 2002
    The overall goal of this project is to improve the effectiveness of camptothecin through a clearer understanding of the cellular roles of topoisomerase I...
    HERBERT GELLER; Fiscal Year: 2000
    ..proteins in apoptosis of cultured rat CNS neurons after DNA damage by irradiation or treatment with camptothecin. We will first determine the changes in immediate early genes (IEGs) and cell cycle-related proteins (cyclin- ..
    THOMAS MC KNIGHT; Fiscal Year: 1999
    ..the mechanisms by which Camptotheca acuminata regulates the biosynthesis, transport, and degradation of camptothecin (CPT), an antitumor and antiviral alkaloid...
  51. ABC Transporters in CNS Penetration of Camptothecins
    Christopher Waters; Fiscal Year: 2007
    ..b>Camptothecin analogs such as topotecan and irinotecan are used to treat children with primary CNS tumors, but the CNS ..
  52. SUMOylation and Cell Sensitivity to Top1 Poisons
    Mary Ann Bjornsti; Fiscal Year: 2009
    ..Top1p is also the target of camptothecin (CRT), which reversibly stabilizes a covalent enzyme-DNA intermediate...
  53. DNA Minor Groove-Targeting Anticancer Agents
    DANIEL PILCH; Fiscal Year: 2006
    ..TB derivatives exhibit potent TOP1 poisoning activities and cytotoxicities exceeding that of the clinical camptothecin derivative, topotecan...
  54. A Two Hybrid System Based Yeasy Screen for Agents that Affect DNA Damage Checkpoi
    Nalin Kumar; Fiscal Year: 2007
    ..compounds that enhance (or diminish) the checkpoint-activating effect of the established chemotherapy drug camptothecin. It is expected that the usefulness of this agent class of topoisomerase I inhibitors can be enhanced by ..
    Daniel Von Hoff; Fiscal Year: 2001
    ..3. To develop camptothecin analogs that have stabilized lactone rings, thereby preventing pH-dependent ring opening and deactivation of ..
  56. Coupling of 5-HT Receptors to Neuroprotective Pathways
    DANIEL COWEN; Fiscal Year: 2007
    ..induced by two well-studied inducers of apoptosis: 1) nitroprusside (through nitric oxide toxicity) and 2) camptothecin (through DNA damage)...
    ARTHUR PARDEE; Fiscal Year: 1993
    ..Consistent with this, we showed that camptothecin, a specific inhibitor of topoisomerase I, also enhanced the lethality of DNA damage in cells...
  58. Combinatorial Development of Blood Stable Camptothecins
    Bradley Anderson; Fiscal Year: 2004
    ..Two camptothecin analogs are already on the market and a number of others are in various stages of research and development...
    Howard Hochster; Fiscal Year: 1993
    The goal of this project is to elucidate the mechanism of action of camptothecin analogs as topoisomerase poisons in upper GI cancer patients...
  60. Development of Novel Polymeric Prodrugs of Camptothecin
    Thomas Schluep; Fiscal Year: 2005
    20(S)-camptothecin (CPT) is a natural product with potent anti-tumor activity and two CPT analogs have been approved as anticancer treatments. However, CPT is insoluble, poorly stable and can cause significant toxicities...
  61. Structure and Mechanism of Human Topoisomerase I
    MATTHEW REDINBO; Fiscal Year: 2004
    ..Specific phases of this mechanism are targeted by the anti-cancer drug camptothecin. Second, determine the structural basis for the camptothecin resistance and hypersensitivity conferred by ..
    MONORE WALL; Fiscal Year: 1990
    ..In order to extend the clinical applicability of our most active camptothecin compounds which are water insoluble, we propose to prepare water soluble analogs which in many cases would be ..
    Nicholas Donato; Fiscal Year: 1999
    ..suggested that increased cellular apoptotic sensitivity to DNA-interactive drugs like cis-platinum (cDDP) and camptothecin (CPT) is associated with high expression of EGFr and a reduction in DNA repair capacity...
  64. Camptothecin Analogs for Cancer Therapy
    LEE MORGAN; Fiscal Year: 2007
    ..Prior to the latter, DEKK-TEC proposes screening the analogs in a wide spectrum of tumor models to insure the best cancer applications for the products. [unreadable] [unreadable] [unreadable]..