Wiki: Poly ADP ribose polymerase: Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death.
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Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery - Variability of Poly (ADP-Ribose) Polymerase Activity.Abstract
Purpose:
The aim of this study was to
evaluate the feasibility of phase 0 trials in the setting of a routine
surgical procedure.
Logistic considerations, tissue sampling and
handling, and variability of a biomarker during surgery, in here
activity of
poly(ADP-ribose) polymerase, were evaluated.
Experimental design:
Patients with highly
suspicious or proven diagnosis of advanced ovarian cancer, planned for
debulking
surgery were asked to allow sequential tumor
biopsies during surgery. Biopsies were frozen immediately and poly
(ADP-ribose)
polymerase activity was measured subsequently.
Results:
Baseline biopsies were obtained from eight
patients after a median time of 88 minutes (minimum of 50 to maximum of
123 minutes). Second and third biopsies were
obtained after a median of 60 (32-96) and 101 (79-130) minutes,
respectively.
Mean tumor load was 44% (5%-100%), with a cellular
viability of 98% (85%-100%). Median baseline PARP activity was 1035
pg/ml
(range: 429-2663 pg/ml). The observed inter-patient
variability at baseline was large: standard deviation was 769 before
and
0.59 after natural log transformation.
Conclusions:
Conducting phase 0 trials during
surgery seems to be feasible in terms of logistic considerations. In
preparation
of a phase 0 trial during surgery, a feasibility
study like this should be conducted to rule out major interactions of
the
surgical intervention with respect to the targeted
biomarker.
