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Record W2060388290 · doi:10.1182/blood-2013-09-526392

Asparaginase unveils glutamine-addicted AML

2013· letter· en· W2060388290 on OpenAlexaff
Ismael Samudio, Marina Konopleva

Bibliographic record

VenueBlood · 2013
Typeletter
Languageen
FieldMedicine
TopicAcute Lymphoblastic Leukemia research
Canadian institutionsTerry Fox Research Institute
Fundersnot available
KeywordsMedicineGlutamineAsparaginaseInternal medicineLeukemiaChemistryLymphoblastic LeukemiaBiochemistry

Abstract

fetched live from OpenAlex

evaluated for the treatment of hematologic malignancies are listed in the table.The ADC used in this study by Deckert et al comprises a humanized anti-CD37 antibody, K7153A, linked via a SMCC [N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate] linker to the maytansinoid DM1 payload.DM1 exerts its antimitotic effect by depolymerizing microtubules and arresting the cells in prometaphase/metaphase.The authors go on to dissect in detail the antitumor mechanism of the DM1-conjugated antibody (IMGN529), demonstrating that the conjugated compound retains the same strong immune effector activities as the unconjugated K7153A.When the naked K7153A and IMGN529 were compared in cytotoxicity assays, the cytotoxic potency induced by IGMN529 was far superior compared with the naked antibody, with induction of cell death in a dose-dependent manner in the picomolar range.Mice inoculated with a human B-cell lymphoma cell line receiving single doses of IMGN529 had a better tumor-free survival time than mice treated with the unconjugated antibody or with rituximab, confirming the additive effect of DM1 delivery.B-cell depletion was observed in the treated animal, and it was more profound than that induced by rituximab treatment.Given these results, IMGN529 seems to be a promising drug, and certainly the planned first-in-man clinical trial is warranted.Overall, the success of trastuzumab-emtansine, as well as that of brentuximab vedotin, suggests that ADCs might take a spotlight in the current landscape of anticancer drugs.

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.

How this classification was reachedexpand

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 categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesResearch integrity, Insufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Commentary · Consensus signal: Commentary
Teacher disagreement score0.077
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0030.006

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 head0.016
GPT teacher head0.259
Teacher spread0.243 · 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

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreCommentary

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".

Quick stats

Citations23
Published2013
Admission routes1
Has abstractyes

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