title: Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report.
abstract: OBJECTIVE
  Omeprazole (OPZ) and tamoxifen (TAM) strengthen the effects of anticancer drugs and dichloroacetate (DCA) inhibits tumor growth. This study assesses the synergistic effects of these drugs.
  
  
  METHODS
  HT1080 human fibrosarcoma cells and WI-38 human fibroblasts were used as test and control cells, respectively. DCA, OPZ and TAM alone or in combination were applied and cells were counted after a one week culture. The combination of these drugs was prescribed to a cholangiocarcinoma patient and serum CA19-9 was monitored.
  
  
  RESULTS
  DCA combined with OPZ and TAM exhibited more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells, but did not influence proliferation of WI-38 human fibroblasts. All these drugs induce caspase-dependent cell growth inhibition through superoxide production. Since they can be taken orally and have been used clinically without major side effects, it was thought that this combination therapy would be a readily translated strategy to treat malignant tumors. Under the patient's consent these three drugs were prescribed to a 51-year old female cholangiocarcinoma patient to whom neither gemcitabine+S-1 nor adoptive immunotherapy with natural killer cells was effective. Disease progression was successfully blocked (the rise of serum CA19-9 value) for three months, also confirmed by CT.
  
  
  CONCLUSIONS
  Although findings are preliminary, this study is a sample of translational research. Since there is no consensus regarding treatment strategy of cholangiocarcinoma and chemotherapy has only limited efficacy, it is expected that it might open a new possibility of treatment.
authors.affiliation: Kamui Medical CO., Ltd., Tokyo, Japan. ti227241@ka3.so-net.ne.jp
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Ishiguro
authors.forename: Ryumei
authors.initials: R
authors.lastname: Ishiguro
authors.forename: Miyu
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Sayuri
authors.initials: S
authors.lastname: Iwai
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D003999:Dichloroacetic Acid / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D013629:Tamoxifen; D003999:Dichloroacetic Acid; D009853:Omeprazole