title: Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas.
abstract: OBJECTIVE
  Antitumour treatments are thought to exert their therapeutic efficacy mainly by induction of apoptosis in tumour cells. In epithelial cells, caspases, the key enzymes of apoptosis, cleave the intermediate filament protein cytokeratin (CK)-18 into specific fragments that are released into circulating blood and can be detected by a specific ELISA.
  
  
  METHODS
  To investigate the use of CK-18 fragments as a potential biomarker for the treatment response, we examined the association of serum CK-18 levels and clinical response in 35 patients with gastrointestinal cancers.
  
  
  RESULTS
  While both cleaved and total CK-18 levels were intrinsically elevated in tumour patients, they were further increased during 5-fluorouracil (5-FU)-based therapy. Importantly, the increased levels of CK-18 could discriminate between patients with different clinical response. Cancer patients with a partial response or stable disease revealed a significantly higher increase of cleaved CK-18 during chemotherapy as compared to patients with progressive disease.
  
  
  CONCLUSIONS
  Our results suggest that detection of circulating caspase-cleaved CK-18 might be a useful serum biomarker for monitoring treatment response and should merit further evaluation in larger patient groups.
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Brandt
authors.forename: Xandra
authors.initials: X
authors.lastname: Volkmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Anstätt
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D016903:Drug Monitoring / Q000379:methods; D004789:Enzyme Activation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D020169:Caspases