ABSTRACT
Lymph node metastasis is often the first indication of the aggressiveness of breast cancer. Effective chemotherapy in breast cancer depends on targeting the metastatic component of the disease. In order to optimize chemotherapy in the metastatic target of breast cancer, the histoculture drug response assay (HDRA) was performed on surgical specimens of primary tumor and axillary lymph node metastasis from 30 breast cancer patients. The surgical specimens were cut into approximately 10 mg pieces, and placed onto the collagen gel sponges in the medium containing previously-determined cutoff concentrations of doxorubicin (DXR), 5-fluorouracil (5-FU), cisplatin (DDP), and mitomycin C (MMC). After incubation for 7 days, the chemosensitivity of the tumor fragments was evaluated with the 3-(4,5-dimethythiazol2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) endpoint. The lymph node metastases were more resistant than the primary tumor for DXR, 5-FU, and MMC (p < 0.05) but not for CDDP. The data suggest that both primary tumor and metastases from individual patients should be tested in the HDRA to enhance clinical efficacy of chemotherapy.
Subject(s)
Antineoplastic Agents/toxicity , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cisplatin/toxicity , Doxorubicin/toxicity , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Female , Fluorouracil/toxicity , Humans , Lymph Node Excision , Lymphatic Metastasis/pathology , Mitomycin/toxicity , Tumor Cells, CulturedABSTRACT
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.
