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Updated: Oct 26, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Antitumor spectra of anthracyclines against gastric cancer tissues obtained from surgical specimens with reference to
T Furukawa1, T Kubota, H Murata
1Immunochemical Laboratory, Eiken Chemical Co., Ltd. Tokyo, Japan. tomokof@pb3.so-net.ne.jp
Background And Objectives:
Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression.
Methods:
Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP.
Results:
A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR.
Conclusions:
The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.
Insights
P-glycoprotein (Pgp) expression confers resistance to doxorubicin (DXR) and epirubicin (EPI) in gastric cancer. Pirarubicin (THP) may overcome this resistance, showing potential clinical utility for DXR-refractory cases.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- P-glycoprotein (Pgp) mediated resistance is known for doxorubicin (DXR), but not fully understood for other anthracyclines.
- Gastric cancer exhibits variable responses to anthracycline chemotherapy.
- Understanding drug resistance mechanisms is crucial for optimizing cancer treatment.
Purpose of the Study:
- To investigate the chemosensitivity of gastric cancer tissues to three anthracyclines: doxorubicin (DXR), epirubicin (EPI), and pirarubicin (THP).
- To correlate the chemosensitivity with P-glycoprotein (Pgp) expression in gastric cancer specimens.
Main Methods:
- Histoculture drug response assay (HDRA) was performed on 66 gastric cancer surgical specimens.
- Drugs tested included DXR, EPI, and THP at specific cutoff concentrations.
- Immunohistochemistry was used to detect Pgp expression in 26 of the specimens.
Main Results:
- High correlation in sensitivity was observed between DXR and EPI (95.8%).
- Pgp-positive specimens showed universal resistance to DXR and EPI.
- Pirarubicin (THP) demonstrated partial sensitivity in 28.6% of Pgp-positive cases, unlike DXR and EPI.
Conclusions:
- Pgp expression significantly contributes to DXR and EPI resistance in gastric cancer.
- Pirarubicin (THP) may offer a viable therapeutic option for DXR-refractory gastric carcinomas due to its ability to partially overcome Pgp-mediated resistance.
- Further clinical evaluation of THP in this context is warranted.
