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*

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

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

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

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

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: Numerous non-invasive imaging methods for evaluating the chemotherapy response of breast cancer patients are currently being explored. The aim of present study was to investigate whether the washout rates (WRs) of 99mTc-MIBI could predict the response to chemotherapy in patients suffering with infiltrating ductal carcinoma using the expressions of multidrug resistance-related protein (MRP) and P-glycoprotein (Pgp). METHODS: From May 2002 and March 2004, the patients were randomly and consecutively selected according to the results of immunohistochemical analyses of breast carcinoma specimens before the administration of neoadjuvant chemotherapy. A total 45 infiltrating ductal carcinomas in 45 female patients were selected and they were separated into three groups: group A consisted of tumors with both negative Pgp and MRP expressions (n=15); group B consisted of the tumors that were positive for either a Pgp expression or a MRP expression (n=15); group C consisted of the tumors that were positive for both Pgp and MRP expressions (n=15). All the patients were referred for double phase 99mTc-MIBI mammoscintigraphy after the injection of 925 MBq of 99mTc-MIBI to calculate the WR. The tumor response was evaluated after completion of neoadjuvant chemotherapy. The tumor response was classified as a complete or partial response (the responder group) and stable or progression (the non-responder group). All the patients underwent surgery. RESULTS: The response rate of group C was lower than that of the other groups, but the difference was not statistically significant (p=0.283). The WR of non-responder group was lower than that of the responder group, although the difference was not statistically significant (p=0.674). The washout rates of group C was the highest than other groups and the difference was statistically significant (p=0.001). CONCLUSION: In conclusion, the WR of 99mTc-MIBI is helpful for in vivo determination of both the Pgp and MRP expressions for infiltrating ductal carcinoma of the breast.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Drug Therapy* ; Female ; Humans ; P-Glycoprotein*