Extranodal NK/T-cell lymphoma (ENKL) is a rare subtype of NHL (Non-Hodgkin lymphoma]. It occurs mostly in the nasal and paranal areas. Most of the cases are presented stage I/II. International prognostic index (IPI) can predict the outcome. However, better prognostic model is available such as NKIPI. Because of high expression of p-glycoprotein, ENKL is refractory to chemotherapy. Early stage disease can be bestly treated with concurrent chemoradiation. For advanced stage disease, new clinical trials are now being conducted.
Lymphoma ; P-Glycoprotein

No abstract available.
P-Glycoprotein* ; Stomach Neoplasms*

No abstract available.
Breast* ; DNA* ; P-Glycoprotein*

No abstract available.
Leukemia, Monocytic, Acute* ; P-Glycoprotein*

No abstract available.
Carcinoma, Transitional Cell* ; Humans* ; P-Glycoprotein* ; Urinary Bladder*

Oseltamivir is a substrate of P-glycoprotein, an efflux drug transporter encoded by ABCB1. The objective of this study was to assess the role of ABCB1 (c.1236C>T, c.2677G>T/A, and c.3435C>T) polymorphisms in the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate in humans. Nineteen healthy male subjects were enrolled, and their ABCB1 polymorphisms were evaluated. After the oral administration of 75 mg oseltamivir, the plasma concentrations of oseltamivir and oseltamivir carboxylate were measured. Pharmacokinetic analysis was carried out. Systemic exposure to oseltamivir and oseltamivir carboxylate was higher in the mutant group than in the wild-type and heterozygous groups. We suggest that ABCB1 polymorphisms affect the pharmacokinetics of oseltamivir in humans. Further studies in a large population are necessary to validate the results of this preliminary study (Clinical Trial Registration Information [CRIS] registry: http://cris.nih.go.kr, No. KCT0001903).
Administration, Oral ; Humans* ; Male ; Oseltamivir* ; P-Glycoprotein ; Pharmacokinetics* ; Plasma

OBJECTIVE: We determined the influence of 3-OMD in the protein binding of levodopa to estimate the effect of 3-OMD on the penetration of levodopa into brain. METHOD: P-glycoprotein in the brain may serve to limit drug penetration into the brain. Because it is not available as an experimental substance, but has similar binding properties with alpha 1 acid glycoprotein(AGP), we used AGP in this study. Additionally, we used blood plasma to see the affinity of plasma binding of levodopa. The final concentration of chemicals used in this study were 125, 250, 500, 1000, 2000, 4000 microgram/l for levodopa and 0, 1250, 5000, 10,000 microgram/l for 3-OMD, 1 mg/l for AGP. The free fraction of levodopa in blood plasma and AGP were separated by ultrafiltration method and determined by beta-counter, respectively. RESULTS: We found that levodopa did not bind with AGP, but only 22-24% from 125 microgram/l to 4000 microgram/l of it bound with blood plasma. The addition of 3-OMD to the blood plasma did not significantly change the binding of levodopa. CONCLUSIONS: We can conclude that 3-OMD does not influence the penetration of levodopa into brain. These small amount of the binding does not expect to influence to other drugs on the binding with plasma.
Brain ; Drug Interactions ; Levodopa* ; P-Glycoprotein ; Plasma* ; Protein Binding ; Ultrafiltration

PURPOSE: Despite the fact that the primary factor to determine the prognosis of breast cancer is the metastatic lesion rather than the primary tumor, most studies concerning the prognostic factors related with tumoric biological behavior have focused on the primary tumors. A better understanding of changes of biological behavior in the metastatic lesions will provide a clue to more effective and rational approaches for treating metastatic breast cancer. METHODS: This study was designed to investigate the biological characteristics of metastatic cancer cells in breast cancer and to compare them to those of the primary tumors. Eighty-two breast cancer patients with metastatic axillary lymph nodes were selected for study. The evaluated tumoric biological characteristics used in this study were histologic grade, estrogen receptor, progesterone receptor, bcl-2, c- erbB2, p53, and P-glycoprotein. Evaluations were carried out with H-E and immunohistochemical stainings. The subjects were divided into positive cases and negative cases, according to extent and degree of staining. McNemar's test and Spearman's rho correlation coefficient were used for statistical analysis and cases showing a p-value of 0.05 or less were taken as being statistically significant. RESULTS: The results were as follows: 1) Metastatic nodes showed higher histologic grade than primary tumors. 2) No significant pattern was observed concerning changes in biological characteristics, including estrogen receptor, progesterone receptor, bcl-2, c-erbB2, p53, and P-glycoprotein between primary tumor and metastatic lymph nodes. 3) Neither wea any significant difference observed in biological behavior among the metastatic lymph nodes. CONCLUSION: This results indicate that the meaningful biological characteristic of metastatic lesion is higher histologic grade alone, and suggest that this change in histologic grade is the single, specific factor determineing the prognosis for metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Estrogens ; Humans ; Lymph Nodes* ; P-Glycoprotein ; Population Characteristics ; Prognosis ; Receptors, Progesterone

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a dose-limiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration-time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.
Absorption ; Humans ; Maximum Tolerated Dose ; Neutropenia ; P-Glycoprotein* ; Paclitaxel* ; Pharmacokinetics ; Plasma

It is deirable to identify the tumoric factors anticipating the therapeutic failure in breast cancer patients received postoperative adjuvant chemotherapy. So, we studued the tumoric topoisomerase II alpha enzyme, c-erbB-2 oncoprotein, and Pgp expression in breast cancer tissues to identify the roles of these factors as the predictors of chemotherapeutic result. The results were as follows. 1) There wee no significant differences in the average value of topoisomerase II alpha enzyme, c-erb B-2 oncoportein overexpression, and Pgp expression according to stages. 2) CAF chemotherapy was suggested to be more effective than CMF chemotherapy in more advance stages. 3) There was a possible suggestion that the breast cancer with high topoisomerase II alpha enzyme activity might indicate the failure with CMF chemotherapy. 4) C-erbB-2 oncoportein overexperession suggested the possibility of therapeutic failure with CMF chemotherapy and the selection of CAF chemotherapy might improve the survival of advanced breast cancer patients with c-erbB-2 overexpression. In conclusion, it was suggested that c-erb-2 oncopotein overexpression and high topoisomerase II alpha activity might have a meaningful role in the selection of proper chemotherapeutic regimen in setting of adjuvant chemotherapy and predict the therapeutic failure of some chemotherapeutic agents for breast cancer. An expanded study for these factors is required to reveal the clinical significance in chemotherapy for breast cancer patients.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; DNA Topoisomerases, Type II* ; Drug Therapy* ; Humans ; P-Glycoprotein*