PURPOSE: A large body of evidence implicates apoptosis in the effects of cancer chemotherapeutic agents on tumor cells in vitro and tumor xenografts in vivo, but the predictive value of apoptosis as an early marker for clinical response in cancer patients remains unclear. EXPERIMENTAL DESIGN: We developed an automated, laser scanning cytometer-based method to quantify the percentage of tumor cells containing DNA fragmentation characteristic of apoptosis in tumor sections. We measured levels of apoptosis in a panel of 15 matched, 18-gauge core breast cancer biopsies obtained before and 48 h after neoadjuvant therapy with docetaxel plus doxorubicin or paclitaxel as part of two prospective clinical trials. RESULTS: The results revealed a strongly significant (P = 0.0023) association between chemotherapy-induced apoptosis and pathological response. CONCLUSIONS: If the results can be validated in a larger patient cohort, the method could be used to "tailor" therapy to optimize benefit in a patient-specific fashion.
PURPOSE: A large body of evidence implicates apoptosis in the effects of cancer chemotherapeutic agents on tumor cells in vitro and tumor xenografts in vivo, but the predictive value of apoptosis as an early marker for clinical response in cancerpatients remains unclear. EXPERIMENTAL DESIGN: We developed an automated, laser scanning cytometer-based method to quantify the percentage of tumor cells containing DNA fragmentation characteristic of apoptosis in tumor sections. We measured levels of apoptosis in a panel of 15 matched, 18-gauge core breast cancer biopsies obtained before and 48 h after neoadjuvant therapy with docetaxel plus doxorubicin or paclitaxel as part of two prospective clinical trials. RESULTS: The results revealed a strongly significant (P = 0.0023) association between chemotherapy-induced apoptosis and pathological response. CONCLUSIONS: If the results can be validated in a larger patient cohort, the method could be used to "tailor" therapy to optimize benefit in a patient-specific fashion.
Authors: Monika Graeser; Afshan McCarthy; Christopher J Lord; Kay Savage; Margaret Hills; Janine Salter; Nicholas Orr; Marina Parton; Ian E Smith; Jorge S Reis-Filho; Mitch Dowsett; Alan Ashworth; Nicholas C Turner Journal: Clin Cancer Res Date: 2010-08-27 Impact factor: 12.531
Authors: Quang-Dé Nguyen; Graham Smith; Matthias Glaser; Meg Perumal; Erik Arstad; Eric O Aboagye Journal: Proc Natl Acad Sci U S A Date: 2009-09-03 Impact factor: 11.205
Authors: William H Goodson; Maria Gloria Luciani; S Aejaz Sayeed; Ian M Jaffee; Dan H Moore; Shanaz H Dairkee Journal: Carcinogenesis Date: 2011-09-01 Impact factor: 4.944
Authors: Fares Al-Ejeh; Jocelyn M Darby; Chris Tsopelas; Douglas Smyth; Jim Manavis; Michael P Brown Journal: PLoS One Date: 2009-02-27 Impact factor: 3.240
Authors: C D Archer; M Parton; I E Smith; P A Ellis; J Salter; S Ashley; G Gui; N Sacks; S R Ebbs; W Allum; N Nasiri; M Dowsett Journal: Br J Cancer Date: 2003-09-15 Impact factor: 7.640