Disease relevance of SLC1A4

• Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas [1].
• These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types [1].
• Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT [2].
• We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor-risk aggressive lymphoma [3].
• A prospective randomized study comparing high-dose therapy and ASCT with conventional chemotherapy in IPI high-risk patients with aggressive non-Hodgkin's lymphoma should be undertaken [3].

Psychiatry related information on SLC1A4

• CONCLUSIONS: Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT [4].
• Changes in region- and cell type-specific expression patterns of neutral amino acid transporter 1 (ASCT-1) in the anterior cingulate cortex and hippocampus in schizophrenia, bipolar disorder and major depression [5].

High impact information on SLC1A4

• In the non-HIV setting, patients with relapsed Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) have a better chance of long-term remission with high-dose chemotherapy with autologous stem cell rescue (ASCT) compared with conventional salvage chemotherapy [6].
• These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma [3].
• Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV) [7].
• Patients 60 years or younger with progressive lymphoma were eligible to receive HDCT with ASCT [8].
• A great improvement was found in the ASCT group (P<.01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group [9].

Chemical compound and disease context of SLC1A4

• A phase I-II study of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) for B cell non-Hodgkin's lymphoma prior to and after high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) [10].
• This phase I-II study describes the safety of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) as an induction regimen prior to high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), and rituximab given post-HDC-ASCT for B cell non-Hodgkins's lymphoma [10].
• The purpose of this study was to evaluate the morbidity and mortality of RSV infections in patients with multiple myeloma undergoing ASCT without ribavirin therapy [11].
• BACKGROUND AND OBJECTIVES: High-dose melphalan with autologous peripheral blood stem cell transplantation (ASCT) is an effective treatment for systemic primary amyloidosis [12].
• In an effort to minimise induction therapy-related toxicity, avoid unnecessary hospitalisation and facilitate early ASCT, we have prospectively evaluated an outpatient-based oral chemotherapeutic regimen, cyclophosphamide, idarubicin, dexamethasone (CID) in patients with previously untreated multiple myeloma (mm) [13].

Biological context of SLC1A4

• Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15 [14].
• The putative protein, designated SATT, is 529 amino acids long and exhibits significant amino acid sequence identity (39-44%) with mammalian L-glutamate transporters [15].
• Expressed human hippocampal ASCT1 amino acid transporter exhibits a pH-dependent change in substrate specificity [16].
• Following transfection of HeLa cells with the ASCT1 cDNA, transport strongly favored neutral zwitterionic) amino acids when uptake was measured at a physiologic pH value of 7 [16].
• A dose-dependent study of glutamate in astrocytes of SHRSP indicated differences in the secretion of l-Ser, and gene expression of PHGDH and ASCT1, compared with levels in the WKY astrocytes [17].

Anatomical context of SLC1A4

• SATT expression in HeLa cells did not induce the transport of radiolabeled L-cysteine, L-glutamate, or related dicarboxylates [15].
• Northern blot hybridization revealed high levels of SATT mRNA in human skeletal muscle, pancreas, and brain, intermediate levels in heart, and low levels in liver, placenta, lung, and kidney [15].
• SATT may represent one of multiple activities that exhibit System ASC-like transport characteristics in diverse tissues and cell lines [15].
• In contrast to Gln uptake, Thr uptake was more active in cells cultured in the absence of Gln and showed neither pH dependence nor lithium tolerance in either medium, which is typical of an uptake mediated by the widespread ASCT1 isoform of system ASC [18].
• In contrast, the profile for rat astrocytes was a mixture of that for HEK293 cells expressing rat ASCT1 and that for the cells expressing rat ASCT2 [19].

Associations of SLC1A4 with chemical compounds

• Expression of SATT cDNA in HeLa cells induced stereospecific uptake of L-serine, L-alanine, and L-threonine that was not inhibited by excess (3 mM) 2-(methylamino)-isobutyric acid, a specific substrate for the System A amino acid transporter [15].
• Screening for cDNAs encoding proteins similar to the sodium-coupled glutamate transporter GLAST1 led to the isolation of a cDNA clone coding for a protein that turned out to be identical to the recently described neutral amino acid transporter ASCT1 [14].
• 5. However, lowering the assay pH to 5.5 significantly enhanced the interaction of the ASCT1 carrier with anionic amino acids such as cysteate, in a pH-dependent manner [16].
• ASCT-1 is a neutral amino acid exchanger with chloride channel activity [20].
• ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg) [2].

Other interactions of SLC1A4

• ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous [1].
• RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen [2].
• ASCT1 is a member of the glutamate transporter superfamily cloned from human brain and characterized as a Na(+)-dependent neutral amino-acid exchanger, which displays substrate-induced chloride-channel activity and mediates concentrative transport of alanine [21].

Analytical, diagnostic and therapeutic context of SLC1A4

• With long-term follow-up we demonstrate that ASCT can lead to an 85% progression-free survival, which suggests that this approach may be potentially curative in select patients with relapsed HIV-associated HD or NHL [6].
• PURPOSE: To evaluate health-related quality of life (HRQOL) in adults treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem-cell transplantation 1 year after transplantation, using data from concurrent lymphoma patients receiving combination chemotherapy (CT) as a reference [9].
• Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease [22].
• High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas [23].
• The purpose of this study was to investigate the role of autologous peripheral blood stem cell transplantation (ASCT) for the treatment of WM [24].

References