title: Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy.
abstract: Despite significant progress in cancer therapy, the outcome of the treatment is often unfavorable. Better treatment monitoring would not only allow an individual more effective, patient-adjusted therapy, but also it would eliminate some of the side effects. Using a cytochrome c ELISA that was modified to increase sensitivity, we demonstrate that serum cytochrome c is a sensitive apoptotic marker in vivo reflecting therapy-induced cell death burden. Furthermore, increased serum cytochrome c level is a negative prognostic marker. Cancer patients whose serum cytochrome c level was normal 3 years ago have a twice as high probability to be still alive, as judged from sera samples collected for 3 years, analyzed recently and matched with survival data. Moreover, we show that serum cytochrome c and serum LDH-activity reflect different stages and different forms of cell death. Cellular cytochrome c release is specific for apoptosis, whereas increased LDH activity is an indicator of (secondary) necrosis. Whereas serum LDH activity reflects the "global" degree of cell death over a period of time, the sensitive cytochrome c-based method allows confirmation of the individual cancer therapy-induced and spontaneous cell death events. The combination of cytochrome c with tissue-specific markers may provide the foundation for precise monitoring of apoptosis in vivo, by "lab-on-the-chip" technology.
authors.affiliation: Department of Immunology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Barczyk
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.forename: Juliusz
authors.initials: J
authors.lastname: Pryjma
authors.forename: Evan P
authors.initials: EP
authors.lastname: Booy
authors.forename: Subbareddy
authors.initials: S
authors.lastname: Maddika
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Marek
authors.initials: M
authors.lastname: Los
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood*; D045304:Cytochromes c / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D045304:Cytochromes c