Evidence map›Paper›PMID 42491925›Full record

ArticleJapanese journal of cancer and oncology research2025

Chondrosarcoma: Adjuvant Therapeutic Effects of the ASPH Small Molecule Inhibitor, SMI-1182, With Doxorubicin.

Keisuke Oyama, Megan Fife, Rolf I Carlson, Ming Tong, Yoshihiro Matsumoto, Yuki Yokota, Bhaskar Das, Parthiban Chokkalingam, Rene Rodriguez, Suzanne M de la Monte

Abstract read
In one paragraph

Article in Japanese journal of cancer and oncology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Keisuke OyamaDepartment of Orthopedic Surgery and Gastroenterological Surgery, Rhode Island Hospital, Alpert Medical School at Brown University, USA and Graduate School of Medicine, Osaka University, Osaka, Japan.
Megan FifeMolecular Pharmacology, Physiology, and Biotechnology Graduate Program at Brown University, USA.
Rolf I CarlsonDepartment of Medicine, Rhode Island Hospital, Alpert Medical School at Brown University, USA.
Ming TongDepartment of Medicine, Rhode Island Hospital, Alpert Medical School at Brown University, USA.
Yoshihiro MatsumotoDepartment of Medicine, Rhode Island Hospital, Alpert Medical School at Brown University, USA.
Yuki YokotaDepartment of Medicine, Rhode Island Hospital, Alpert Medical School at Brown University, USA.
Bhaskar DasDrug and Biotherapeutic Discovery University at Buffalo, The State University of New York (SUNY), Buffalo, USA.
Parthiban ChokkalingamDrug and Biotherapeutic Discovery University at Buffalo, The State University of New York (SUNY), Buffalo, USA.
Rene RodriguezHealth Research Institute of Asturias (ISPA), University Institute of Oncology of Asturias (IUOPA), Oviedo, Spain, and CIBER en oncologia (CIBERONC), Madrid, Spain.
Suzanne M de la MonteDepartments of Pathology and Laboratory Medicine, Neurology, and Neurosurgery, Alpert Medical School at Brown University, USA.

Funding

FASD Inhibition of ASPH-Notch Mediates Adolescent Cerebral White Matter Pathology-Potential Utility of Non-invasive Extracellular Vesicle AssaysR01AA011431 · NIAAA · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI SUZANNE M. DE LA MONTE · 1996 to 2026
$5.4M
ASPH Targeted Therapy for ChondrosarcomaR01CA270795 · NCI · RHODE ISLAND HOSPITAL · PI RICHARD M TEREK · 2023 to 2026
$2.6M
Pathogenesis of Early- Versus Late-Stage Alcohol-Mediated White Matter DegenerationR01AA028408 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2021 to 2025
$1.7M
Serum Exosome Detection and Monitoring of Alcohol-Related White Matter Brain Pathology-Opportunities to Optimize Treatment and Monitoring of AUD-Related Organ and Tissue Damage in Diverse PopulationsR21AA032106 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2024 to 2025
$431k
NCI NIH HHS R01 CA270795NIAAA NIH HHS R01 AA011431NIAAA NIH HHS R01 AA028408NIAAA NIH HHS R21 AA032106
6 · The paper itself

Abstract

Chondrosarcoma (CS) is the most common adult malignant bone tumor. Its poor prognosis is due to chemotherapy resistance and high rates of post-treatment recurrence. The finding that CSs express abundant Aspartyl-Asparaginyl-Β-Hydroxylase (ASPH), which drives invasive tumor growth via Notch pathway activation, provides a new opportunity for treatment in combination with standard Doxorubicin (DOX) chemotherapy. We hypothesized that the small-molecule inhibitor SMI-1182, which targets the catalytic domain of ASPH, could enhance the chemotherapeutic effects of DOX by further reducing CS cell viability, motility, and invasive growth. Human CS-1 and CDS11 conventional chondrosarcoma cell lines were treated with broad dose ranges of DOX, SMI-1182, or DOX+SMI-1182 to measure their separate and combined effects on cell viability, toxicity, motility, and invasive growth. Mechanistic studies included assessments of genes and proteins pertinent to ASPH expression and Notch signaling. Treatment with DOX or SMI-1182 caused dose-dependent CS-1 and CDS11 cell loss and cytotoxicity. SMI-1182, with or without DOX, significantly reduced directional motility and invasive growth relative to vehicle. Combined treatments with DOX and SM-1182 had synergistic cytotoxic and anti-invasive growth effects linked to reduced expression of ASPH immunoreactivity, Notch transcription factors, and insulin receptor substrate, type I, which positively regulates both ASPH and Notch. Dual treatment with DOX and SMI-1182 could potentially improve disease-free survival with CS by simultaneous targeting of multiple upstream mediators of aggressive malignant tumor behavior.

Indexed as

Aspartyl-asparaginyl-β-hydroxylaseCancer treatmentChondrosarcomaDoxorubicinNotchSmall molecule inhibitor

Identifiers

PMID42491925
PMCPMC13378441

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.