title: Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and dissecting effects of hyperthermia.
abstract: BACKGROUND
  In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress-mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model.
  
  
  METHODS
  Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells.
  
  
  RESULTS
  Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo.
  
  
  CONCLUSIONS
  Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.
authors: Department of Surgery I, University of Wuerzburg, Wuerzburg, Germany.
authors: Joerg O W
authors: JO
authors: Pelz
authors: Malte
authors: M
authors: Vetterlein
authors: Tanja
authors: T
authors: Grimmig
authors: Alexander G
authors: AG
authors: Kerscher
authors: Eva
authors: E
authors: Moll
authors: Maria
authors: M
authors: Lazariotou
authors: Niels
authors: N
authors: Matthes
authors: Marc
authors: M
authors: Faber
authors: Christoph-Thomas
authors: CT
authors: Germer
authors: Ana Maria
authors: AM
authors: Waaga-Gasser
authors: Martin
authors: M
authors: Gasser
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D010478:Chemotherapy, Cancer, Regional Perfusion; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006979:Hyperthermia, Induced; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D006360:Heat-Shock Proteins; D012333:RNA, Messenger