Purpose: The Rubus coreanus fruit (RF) is an important traditional medicinal herb having antioxidant, anti-inflammatory, and immunoregulatory properties. These activities are known to change dramatically, depending on maturity of the RF. It is presumed that change of functional components, such as flavonoids, tannins, phenolic acids, triterpenoids and organic acids in RF, affect the various bioactivities. This study aimed to confirm changes in the anti-melanogenic effects of RF based on maturity, and to identify the bioactive compounds responsible. Methods: The cell viability of mature RF (MRF) and immature RF (IRF) extracts was investigated using B16F10 cells. To compare the anti-melanogenic effect of MRF and IRF extracts, we first assessed the melanin content. High-performance liquid chromatography analysis was performed to evaluate changes in the level of ellagic acid according to maturity of the RF. In addition, tyrosinase inhibitory activity of both extracts was examined. Results: MRF and IRF extracts (50–200 μg/mL) do not affect the cell viability of B16F10 melanoma cells. IRF extract more effectively inhibited melanin synthesis than MRF extract. The content of ellagic acid in IRF extract was higher than that obtained in MRF extract. Furthermore, greater inhibition of tyrosinase activity was observed after exposure to IRF extract than MRF extract. A positive correlation was determined between ellagic acid content and tyrosinase inhibitory activity, and a negative correlation was obtained between ellagic acid content and melanin content. Taken together, our results indicate that ellagic acid is one of the major bioactive compounds of RF that imparts a whitening effect. Conclusion Our results indicate that ellagic acid in MRF and IRF extracts affect the anti-melanogenesis effect through inhibition of tyrosinase activity. Therefore, the ellagic acid rich IRF has greater potential for application as a natural and functional cosmetic material.

PURPOSE: A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy.
Breast Neoplasms* ; Breast* ; Cisplatin* ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination* ; Fever ; Humans ; Intention to Treat Analysis ; Leukopenia ; Mucositis ; Paclitaxel* ; Pneumonia ; Radiotherapy ; Thrombocytopenia ; Treatment Refusal

We performed a phase II trial to evaluate the efficacy and the safety of gemcitabine monotherapy, a pyrimidine antimetabolite, in patients, who had previously failed anthracycline and taxane-based chemotherapy for the treatment of metastatic breast cancer. MATERIALS AND METHODS: Twenty-one patients with metastatic breast cancer, which was unresponsive to previous chemotherapy, were entered into this study. Gemcitabine was administered at 850 mg/m2, as a 60- minute intravenous infusion on days 1, 8 and 15. This regimen was repeated every 28 days with G-CSF support, but without dose reduction. RESULTS: Objective responses were seen in 6 of the 20 patients who were able to be evaluated (1 complete response and 5 partial responses), with an objective response rate of 30%. The median time to progression was 5 (1~20) months, and the median overall survival duration was 11 (2~21) months. The actual dose intensity was 566.7 mg/m2/wk (range; 340~637.5 mg/m2/wk) and the relative dose intensity was 0.89 (range; 0.40~1.00). Toxicity was mainly hematological. Toxicities included: grade 3 neutropenia in 20% and anemia in 5%. Grades 3 and 4 thrombocytopenia occurred in 15% of the patients. CONCLUSION: Gemcitabine monotherapy is an effective and safe treatment for refractory breast cancer patients heavily treated with the anthracycline and taxane- based regimen.
Anemia ; Breast Neoplasms* ; Breast* ; Drug Therapy ; Granulocyte Colony-Stimulating Factor ; Humans ; Infusions, Intravenous ; Neutropenia ; Thrombocytopenia

BACKGROUND: This study was designed to examine how glutathione, one of the nucleophilic sulfur compounds, effects the cisplatin cellular toxicity in the non-small cell lung cancer cell lines and normal lung epithel ial cell line. METHODS: Three cultured cell lines, the lung adenocarcinoma cell(NCL-H23), the lung squamous carcinoma cell (SK-MES-1) and the normal lung epithelial cell(L-132) line were exposed to various concentrations of cisplation with or without glutathione. The relative viability was estimated as a means of measuring the cisplatin cellular toxicity using the MTT method. RESULTS: In NCL-23, the response to cisplatin was sensitive but glutathione markedly increased the relative survival of the tumor cells by removing the antitumor effect of cisplatin. In both SK-MES-1 and L-132, the responses to cisplatin were less sensitive, and the chemoprotective effect of glutathione compared to an equal cisplatin dose was signigicantly higher in L-132 than in SK-MES-1(p<0.05). CONCLUSION: The protective effects of glutathione on cisplatin-induced cellular toxicity is more signigicant in normal lung epithelial cells than in squamous carcinoma cells.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cell Line* ; Cells, Cultured ; Cisplatin ; Epithelial Cells ; Glutathione* ; Lung ; Sulfur Compounds