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Record W3201108917 · doi:10.21203/rs.3.rs-701601/v1

TumorSelect® Technology Enhancing the Safety and Efficacy of Cancer Chemotherapy

2021· preprint· en· W3201108917 on OpenAlexaff
S J Bannister, Amir E. Wahba, Mahesh Kumar Gundluru, Igor Nikoulin, Douglas L. Rodenburg, Michael Coen, David Lewis, Patrice Penfornis, Pier Paolo Claudio, James D. McChesney

Bibliographic record

VenueResearch Square · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsPrompt (Canada)
Fundersnot available
KeywordsProdrugPaclitaxelToxicityChemotherapyCancerPharmacologyDrugMedicineDrug deliveryCancer cellCancer researchOncologyInternal medicineChemistry

Abstract

fetched live from OpenAlex

Abstract Veiled Therapeutics has developed an anticancer technology, TumorSelect® Technology, which combines proprietary anticancer prodrugs and nanotechnology, which takes advantage from current knowledge of human physiology. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Veiled’s designer prodrugs are assembled within pseudo-LDL nanoparticulates which carry them to tumor tissues where they are taken up, internalized and transformed into active drug and kill the cancer cells. This three-prong approach delivers the anticancer drug selectively to the tumors and thereby avoids or reduces the severe side effect toxicities associated with current chemotherapy. Reduction of side effect toxicity of cancer therapy by our technology will improve patient quality of life, patient retention in treatment regimes, more rapid patient recovery post treatment, and overall patient benefit.A. BackgroundThe costs of cancer, measured in terms of mortality, morbidity, direct costs of treatment, and costs of lost productivity are high.B. MethodsART-207 was synthesized; a pseudo-LDL lipid nanodispersion was formed; and mouse xenograft studies were performed. C. ResultsPreclinical toxicity, efficacy, and distribution data clearly show significant advantages of TumorSelect® paclitaxel over conventional Cremophor® formulations of paclitaxel. These advantages include:· Increased suppression of tumor growth and regrowth· Lower toxicity· Increased survival· Higher number of tumor free animals· Significantly lower concentrations of paclitaxel in non-target tissues· Significantly higher concentrations of paclitaxel in tumor tissueThus, data obtained demonstrated targeted drug delivery and support LDL-receptor dependent mechanism of selective cellular uptake by tumor tissue of TumorSelect® formulated paclitaxel.D. ConclusionsNon-target tissue concentrations of paclitaxel are significantly lower in non-tumored and tumored mice injected with formulated TumorSelect® paclitaxel compared with the mice injected with Cremophor® EL/EtOH (ethanol) paclitaxel (<20%).Tumor concentrations of paclitaxel are significantly higher in tumors of mice injected with formulated TumorSelect® paclitaxel compared with the mice injected with Cremophor® EL/EtOH paclitaxel (194%).Plasma and heart concentrations of paclitaxel are significantly lower in tumored vs. non-tumored animals injected with formulated TumorSelect® paclitaxel (<80%).Selective cellular uptake of TumorSelect® paclitaxel by tumors actively expressing LDL-receptors has been demonstrated.Tumor suppression observed was sustained for 63 days after Q1Dx5 dosing with TumorSelect® paclitaxel.TumorSelect® technology represents a potential major improvement in the clinical treatment of cancer through enhanced efficacy due to tumor-facilitated targeted delivery and reduced patient toxicity with its associated deleterious side effects.

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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.017
GPT teacher head0.359
Teacher spread0.342 · 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

Citations1
Published2021
Admission routes1
Has abstractyes

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