Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
Bibliographic record
Abstract
// Nupur K. Purohit 1, 2, 3 , Rashmi G. Shah 1, 2, 3 , Samuel Adant 1, 2, 3, 4, 5 , Michael Hoepfner 6 , Girish M. Shah 1, 2, 3, * and Jean-Mathieu Beauregard 2, 4, 5, * 1 Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, Canada 2 Cancer Research Center, Université Laval, Quebec City, Canada 3 Neurosciences and Oncology Branches of CHU de Québec, Université Laval Research Center, Quebec City, Canada 4 Department of Radiology and Nuclear Medicine, Université Laval, Quebec City, Canada 5 Oncology Branch of CHU de Québec, Université Laval Research Center, Quebec City, Canada 6 Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany * Senior authorship Correspondence to: Jean-Mathieu Beauregard, email: jean-mathieu.beauregard@chudequebec.ca Keywords: peptide receptor radionuclide therapy; 177 Lu-octreotate; neuroendocrine tumors; PARP inhibitor; radiosensitization Received: November 08, 2017 Accepted: April 06, 2018 Published: May 15, 2018 ABSTRACT For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177 Lu-[DOTA0-Tyr3]-octreotate ( 177 Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177 Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177 Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177 Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177 Lu-octreotate PRRT of NETs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".