title: Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment.
abstract: BACKGROUND
  Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906.
  
  
  METHODS
  Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors.
  
  
  RESULTS
  We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection.
  
  
  CONCLUSIONS
  PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Scott
authors.initials: S
authors.lastname: Bussom
authors.forename: Jinguo
authors.initials: J
authors.lastname: Chen
authors.forename: Courtney
authors.initials: C
authors.lastname: Quinn
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.forename: Wing
authors.initials: W
authors.lastname: Lam
authors.forename: Fulan
authors.initials: F
authors.lastname: Guan
authors.forename: Zaoli
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yichao
authors.initials: Y
authors.lastname: Mark
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhao
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: Jeffrey
authors.initials: J
authors.lastname: White
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D000077146:Irinotecan; D008099:Liver / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008516:Medicine, Chinese Traditional; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; C476037:PHY 906; D012333:RNA, Messenger; D000077146:Irinotecan; D002166:Camptothecin