Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.

BACKGROUND: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer. METHODS: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53. RESULTS: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. CONCLUSIONS: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer.

PURPOSE: (18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer. METHODS: From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake. RESULTS: High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1. CONCLUSIONS: The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation.

Transfer function analysis of positron-emitting tracer imaging system (PETIS) data.

Quantitative analysis of the two-dimensional image data obtained with the positron-emitting tracer imaging system (PETIS) for plant physiology has been carried out using a transfer function analysis method. While a cut leaf base of Chinese chive (Allium tuberosum Rottler) or a cut stem of soybean (Glycine max L.) was immersed in an aqueous solution containing the [18F] F- ion or [13N]NO3- ion, tracer images of the leaf of Chinese chive and the trifoliate of soybean were recorded with PETIS. From the time sequence of images, the tracer transfer function was estimated from which the speed of tracer transport and the fraction moved between specified image positions were deduced.

Real-time [11C]methionine translocation in barley in relation to mugineic acid phytosiderophore biosynthesis.

[11C]Methionine was supplied through barley roots and the 11C signal was followed for 90 min using a real-time imaging system (PETIS), with subsequent development of autoradiographic images of the whole plant. In all cases, [11C]methionine was first translocated to the 'discrimination center', the basal part of the shoot, and this part was most strongly labeled. Methionine absorbed by the roots of the plants was subsequently translocated to other parts of the plant. In Fe-deficient barley plants, a drastic reduction in [11C]methionine translocation from the roots to the shoot was observed, while a greater amount of 11C was found in the leaves of Fe-sufficient or methionine-pretreated Fe-deficient plants. Treatment of Fe-deficient plants with aminooxyacetic acid, an inhibitor of nicotianamine aminotransferase, increased the translocation of [11C]methionine to the shoot. The retention of exogenously supplied [11C]methionine in the roots of Fe-deficient barley indicates that the methionine is used in the biosynthesis of mugineic acid phytosiderophores in barley roots. This and the absence of methionine movement from shoots to the roots suggest that the mugineic acid precursor methionine originates in the roots of plants.

Real time visualization of 13N-translocation in rice under different environmental conditions using positron emitting Ttacer imaging system.

The ammonium ion is an indispensable nitrogen source for crops, especially paddy rice (Oryza sativa L. cv Nipponbare). Until now, it has been impossible to measure ammonium uptake and nitrogen movement in plants in real time. Using the new technologies of PETIS (positron emitting tracer imaging system) and PMPS (positron multi-probe system), we were able to visualize the real time translocation of nitrogen and water in rice plants. We used positron-emitting 13N-labeled ammonium (13NH4+) and 15O-water to monitor the movement. In plants cultured under normal conditions, 13NH4+ supplied to roots was taken up, and a 13N signal was detected at the discrimination center, the basal part of the shoots, within 2 minutes. This rapid translocation of (13)N was almost completely inhibited by a glutamine synthetase inhibitor, methionine sulfoximine. In general, nitrogen deficiency enhanced 13N translocation to the discrimination center. In the dark, 13N translocation to the discrimination center was suppressed to 40% of control levels, whereas 15O-water flow from the root to the discrimination center stopped completely in the dark. In abscisic acid-treated rice, 13N translocation to the discrimination center was doubled, whereas translocation to leaves decreased to 40% of control levels. Pretreatment with NO3- for 36 hours increased 13N translocation from the roots to the discrimination center to 5 times of control levels. These results suggest that ammonium assimilation (from the roots to the discrimination center) depends passively on water flow, but actively on NH4+-transporter(s) or glutamine synthetase(s).

Rapid N transport to pods and seeds in N-deficient soybean plants.

Non-nodulated soybean (Glycine max (L.) Merr.) plants were cultivated hydroponically under N-sufficient (5 mM NaNO(3)) or N-deficient (0.5 mM NaNO(3)) conditions. (13)N- or (15)N- labelled nitrate was fed to the cut end of the stems, and the accumulation of nitrate-derived N in the pods, nodes and stems was compared. Real-time images of (13)N distribution in stems, petioles and pods were obtained using a Positron Emitting Tracer Imaging System for a period of 40 min. The results indicated that the radioactivity in the pods of N-deficient plants was about 10 times higher than that of N-sufficient plants, although radioactivity in the stems and nodes of N-deficient versus N-sufficient plants was not different. A similar result was obtained by supplying (15)NO(3) to cut soybean shoots for 1 h. The fact that the N translocation into the pods from NO(3) fed to the stem base was much faster in N-deficient plants may be due to the strong sink activity of the pods in N-deficient plants. Alternatively, the redistribution of N from the leaves to the pods via the phloem may be accelerated in N-deficient plants. The temporal accumulation of (13)NO(3) in nodes was suggested in both N-sufficient and N-deficient plants. In one (13)NO(3) pulse-chase experiment, radioactivity in the stem declined rapidly after transferring the shoot from the (13)NO(3) solution to non-labelled NO(3); in contrast, the radioactivity in the node declined minimally during the same time period.

Light activates H2 15O flow in rice: Detailed monitoring using a positron-emitting tracer imaging system (PETIS).

Water (H2 15O) translocation from the roots to the top of rice plants (Oryza saliva L. cv. Nipponbare) was visualized over time by a positron-emitting tracer imaging system (PETIS). H2 15O flow was activated 8 min after plants were exposed to bright light (1 500 &mgr;mol m-2 s-1). When the light was subsequently removed, the flow gradually slowed and completely stopped after 12 min. In plants exposed to low light (500 &mgr;mol m-2 s-1), H2 15O flow was activated more slowly, and a higher translocation rate of H2 15O was observed in the same low light at the end of the next dark period. NaCl (80 mM) and methylmercury (1 mM) directly suppressed absorption of H2 15O by the roots, while methionine sulfoximine (1 mM), abscisic acid (10 &mgr;M) and carbonyl cyanide m-chlorophenylhydrazone (10 mM) were transported to the leaves and enhanced stomatal closure, reducing H2 15O translocation.

Production of radioactive endovascular stents by implantation of 133Xe ions.

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the renarrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.