title: Local bacteria affect the efficacy of chemotherapeutic drugs.
abstract: In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy.
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Panos
authors.initials: P
authors.lastname: Lehouritis
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Joanne
authors.initials: J
authors.lastname: Cummins
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Stanton
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Carola T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: Department of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
authors.forename: Florence O
authors.initials: FO
authors.lastname: McCarthy
authors.affiliation: Lawson Health Research Institute, London, Ontario, N6A 4V2, Canada.|Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
authors.affiliation: Lawson Health Research Institute, London, Ontario, N6A 4V2, Canada.|Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Camilla
authors.initials: C
authors.lastname: Urbaniak
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: William L
authors.initials: WL
authors.lastname: Byrne
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Tangney
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001388:Aziridines / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D017338:Cladribine / Q000493:pharmacokinetics* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli / Q000254:growth & development; D005260:Female; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D008087:Listeria / Q000254:growth & development; D051379:Mice; D009368:Neoplasm Transplantation; D012867:Skin / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D003841:Deoxycytidine; D017338:Cladribine; C100099:tretazicar; D014740:Vidarabine; C024352:fludarabine; D000093542:Gemcitabine