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Investigation of the cytotoxcity of novel jadomycins in drug resistant breast cancer cells

2009· article· en· W2285545420 on OpenAlexaff
Kerry B. Goralski, Cathy Graham, Mark E. Issa, David L. Jakeman

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsDalhousie University
Fundersnot available
KeywordsCytotoxicityCancer cellEtoposideDrug resistancePharmacologyDrugCytotoxic T cellBreast cancerMultiple drug resistanceBiologyTransporterCancerCancer researchChemistryChemotherapyBiochemistryMicrobiologyIn vitroGene

Abstract

fetched live from OpenAlex

The drug transporter ABCB1 plays a major role in drug resistance and chemotherapy failure in the treatment of breast cancer. Jadomycins are natural products synthesized by the bacteria S. venezuelae ISP5230 and inhibit the mitotic regulatory protein aurora‐B kinase. The object of our study was to investigate the cytotoxicity of jadomycins towards breast cancer cells. By MTT assay we found that Jadomycin B, DT and G were selectively toxic against MCF7 and T47D breast cancer cells compared to control human kidney (HK2) cells. Jadomycin B, DT and G did not activate ABCB1‐ATPase activity in isolated membrane preparations, suggesting that these molecules may evade the ABCB1 drug resistance transporter. In support of this, Jadomycin B and DT displayed similar cytotoxicity in MCF7 control and taxol resistant MCF7tx400 cells that overexpress ABCB1. Comparatively, MCF7tx400 cells were relatively resistant to the cytotoxic effects of the ABCB1 substrates taxol and etoposide. We conclude that Jadomycin B and DT possess effective chemotherapeutic action against both drug‐sensitive and ABCB1‐expressing drug‐resistant breast cancer cells in culture. This work was supported by the CBCF‐Atlantic chapter.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

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 head0.017
GPT teacher head0.238
Teacher spread0.221 · 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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

Citations0
Published2009
Admission routes1
Has abstractyes

Explore more

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