Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor
Why this work is in the frame
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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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 0.000 |
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 it