L-type Amino Acid Transporter (l-type + amino_acid_transporter)

Distribution by Scientific Domains

Selected Abstracts

Pharmacokinetics of Gabapentin during Delivery, in the Neonatal Period, and Lactation: Does a Fetal Accumulation Occur during Pregnancy?

EPILEPSIA, Issue 10 2005
Inger Öhman
Summary:,Purpose: To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period. Methods: GBP concentrations in plasma and breast milk were determined with high-performance liquid chromatography in samples from six women treated with GBP and in their offspring. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions during 2 days after delivery. GBP concentration also was determined in breast milk and in blood collected from five of the mothers and suckling infants 2 weeks to 3 months after birth. Results: The umbilical cord/maternal plasma concentration ratios ranged from 1.3 to 2.1 (mean, 1.7). GBP plasma concentrations in the neonates declined with an estimated half-life of 14 h. Mean GBP plasma concentrations in the infants were 27% of the cord plasma levels (range, 12,36%) 24 h postpartum. The mean milk/maternal plasma concentration ratio was 1.0 (range, 0.7,1.3) from 2 weeks to 3 months. The infant dose of GBP was estimated to 0.2,1.3 mg/kg/day, equivalent to 1.3,3.8% of the weight-normalized dose received by the mother. The plasma concentrations in the breast-fed infants were ,12% of the mother's plasma levels, but no adverse effects were observed. Conclusions: Our limited observations suggest an active transplacental transport of GBP, with accumulation in the fetus as a consequence. We suggest that this could be by the specific L-type amino acid transporter 1 (LAT-1), which is expressed in the placenta. Newborns seem to have a slightly lower capacity to eliminate GBP than do adults. Transfer of GBP to breast milk is extensive, but plasma concentrations appear to be low in suckling infants. No adverse effects were observed in the newborn. Although more data are needed, our observations suggest that breastfeeding in conjunction with GBP treatment is safe. [source]

Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinoma

Hideaki Kobayashi MD
Abstract Background and Objectives It has been reported that amino acid transport systems play an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. In this study, we investigated whether L-type amino acid transporter 1 (LAT1) is expressed in human non-cancerous esophageal mucosa and esophageal squamous cell carcinoma. We also examined whether LAT1 expression is correlated with histopathological features. Methods From January 1999 to December 2001, sections of formalin-fixed, paraffin-embedded tissue from 11 cases of early esophageal carcinoma (T1) and 19 cases of advanced esophageal carcinoma (T2, T3) were entered in the study. Histopathologically, all 30 cases were squamous cell carcinoma. Immunohistochemical staining was performed using rabbit anti-LAT1 IgG, with the standard avidin-streptavidin immuno-peroxidase method. Measurement was performed by means of computer-assisted image analysis. The ratio of cells with LAT1 expression in esophageal squamous cell carcinoma and non-cancerous esophageal mucosa was used for analysis in this study. Results Non-cancerous esophageal mucosa expressed LAT1 only in the basal layer of the esophageal wall. Esophageal squamous cell carcinoma expressed LAT1 throughout the tumor. LAT1 expression in esophageal squamous cell carcinoma was significantly higher than that in non-cancerous esophageal mucosa. LAT1 expression in esophageal squamous cell carcinoma increased as the depth of invasion progressed (T1,<,T2 (P,=,0.0477), T2,<,T3 (P,=,0.0415), T1,<,T3 (P,=,0.0044)), and as the tumor size increased. Also, high LAT1 expression was significantly associated with well-differentiated carcinoma. Conclusion These results suggest that LAT1 plays a significant role in cell proliferation, differentiation, and invasion in esophageal squamous cell carcinoma. J. Surg. Oncol. 2005;90:233,238. © 2005 Wiley-Liss, Inc. [source]

Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer

CANCER SCIENCE, Issue 4 2009
Kyoichi Kaira
L-[3- 18F]-,-methyltyrosine (18F-FMT) is an amino-acid tracer for positron-emission tomography (PET). We have conducted a clinicopathologic study to elucidate the correlation of angiogenesis with 18F-FMT and 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in patients with non-small cell lung cancer (NSCLC). Thirty-seven NSCLC patients were enrolled in this study, and two PET studies with 18F-FMT and 18F-FDG were performed. Uptake of PET tracers was evaluated with standardized uptake value. Vascular endothelial growth factor (VEGF), CD31, CD34, L-type amino acid transporter 1 (LAT1) and Ki-67 labeling index of the resected tumors were analyzed by immunohistochemical staining, and correlated with the clinicopathologic variables and the uptake of PET tracers. The median VEGF rate was 45% (range, 10,78%). High expression was seen in 30 patients (81%, 30/37). VEGF expression was statistically associated with progressively growing microvessel count. VEGF showed a correlation with LAT1 expression (P = 0.04) and Ki-67 labeling index (P = 0.01). However, it showed no correlation with age, gender, disease stage, tumor size, and histology. Microvessel density (MVD) showed no correlation with any parameters. 18F-FMT and 18F-FDG uptake correlated significantly with VEGF (P < 0.0001, P = 0.026, respectively), whereas the correlation of 18F-FMT and VEGF was more meaningful. The present study demonstrated that the metabolic activity of primary tumors as evaluated by PET study with 18F-FMT and 18F-FDG is related to tumor angiogenesis and the proliferative activity in NSCLC. (Cancer Sci 2009; 100: 753,758) [source]