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Record W4220659921 · doi:10.1016/j.tranon.2022.101390

Single-treatment tumor ablation with photodynamic liposomal irinotecan sucrosulfate

2022· article· en· W4220659921 on OpenAlex
Sanjana Ghosh, Boyang Sun, Dushyant Jahagirdar, Dandan Luo, Joaquı́n Ortega, Robert M. Straubinger, Jonathan F. Lovell

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueTranslational Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicPhotodynamic Therapy Research Studies
Canadian institutionsMcGill University
FundersNational Institute of Biomedical Imaging and Bioengineering
KeywordsLiposomePharmacokineticsPhotodynamic therapyIrinotecanMetaboliteBiodistributionPharmacologyPhotosensitizerChemistryDrugSN-38MedicineCancer researchIn vitroCancerInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Irinotecan (IRI) loaded actively into PEGylated liposomes via a sucrosulfate gradient has been approved recently to treat advanced pancreatic cancer. In this study, a similar liposomal composition was developed that includes a low mole fraction (1 mol.%) of porphyrin-phospholipid (PoP), a photosensitizer that stably incorporates into liposomes, to confer light-triggered IRI release. IRI-loaded PoP liposomes containing ammonium sucrosulfate (ASOS) as a complexing agent were more stable in serum compared to liposomes employing the more conventional ammonium sulfate. Without irradiation, PoP IRI liposomes released less than 5% IRI during 8 h of incubation in bovine serum at 37 °C, but released over 90% of the drug within minutes of exposure to red light (665 nm) irradiation. A single treatment with IRI-PoP liposomes and light exposure (15 mg/kg IRI with 250 J/cm 2 ) resulted in tumor eradication in mice bearing either MIA PaCa-2 tumors or low-passage patient-derived tumor xenografts that recapitulate characteristics of the clinical disease. Analogous monotherapies of IRI or photodynamic therapy were ineffective in controlling tumor growth. Enhanced drug uptake could be visualized within laser-treated tumors by direct in situ imaging of irinotecan. Biodistribution analysis of IRI, its active metabolite (SN-38), and major metabolite (SN-38 G) showed that laser treatment significantly increased tumor accumulation of all IRI-derived molecular species. A pharmacokinetic model that hypothesized tumor vasculature permeabilization as the primary reason underlying the increased drug deposition accounted for the enhanced drug influx into tumors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.784
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.027
GPT teacher head0.317
Teacher spread0.290 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it