|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
A variety of tumor entities depend on the uptake of the amino acid arginine since they have lost the ability to synthesize it endogenously, that is they do not express the rate limiting enzyme for arginine synthesis, argininosuccinate synthase (ASS).
|
31824848 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
However, the progression of arginine non-auxotrophic tumors is independent of exogenous l-arginine, because these tumors have arginine-succinate synthetase (ASS1) activity and are available to produce l-arginine from citrulline.
|
30605863 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The third 6 cm nodule had all the characteristics of an Unclassified HCA with an overexpression of Argininosuccinate Synthase 1 (ASS1) in the tumor compared to the non-tumoral liver.
|
31047837 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
In addition, several tumor types have been shown to downregulate ASS-1 expression, becoming auxotrophic for arginine.
|
31795337 |
2019 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples.
|
29776373 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Depletion of ASS1 led to inhibition of tumor growth and decreased cell invasion via induction of autophagy-lysosome machinery, resulting in degradation of active β-catenin, Snail, and Twist.
|
29401583 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Animals bearing intracranial human GBM tumours of varying ASS status were treated with ADI-PEG20 alone or in combination with temozolomide and monitored for tumour growth and regression.
|
30546006 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Regarding the important role of arginine (Arg) in the regulation of multiple metabolic and signaling pathways, its deprivation has been proposed as a good strategy for tumor regression in tumors with defected Arg metabolic enzymes like argininosuccinate synthase 1 (ASS1).
|
29597093 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Neoplasms that show low to absent ASS1 expression require extracellular arginine for cancer cell survival, and thus can be targeted using arginine-degrading enzymes such as pegylated arginine deiminase (ADI-PEG 20).
|
29453600 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Purpose Pegylated arginine deiminase (ADI-PEG 20) depletes essential amino acid levels in argininosuccinate synthetase 1 (ASS1) -negative tumors by converting arginine to citrulline and ammonia.
|
28388291 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Our findings suggest that ASS1 levels in each tumor cell are associated with invasion capability in response to arginine within the tumor microenvironment through mTORC1 signal regulation.
|
28358054 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
ASS1-low was associated with higher recurrence (p = 0.045), shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001) and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005) in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors.
|
28187218 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These ASS(-) tumors are auxotrophic for arginine.
|
28587170 |
2017 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
ASS1 expression is lost in a range of tumor types, including 50% of malignant pleural mesotheliomas.
|
27452468 |
2016 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Because of decreased expression of argininosuccinate synthetase and/or ornithine transcarbamoylase, several types of tumor are auxotrophic for arginine.
|
27109103 |
2016 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The xenograft models also confirm that BR tumors possess lower expression of ASS1 and are hypersensitive to arginine deprivation.
|
26771234 |
2016 |
|
Neoplasms
|
0.100 |
PosttranslationalModification
|
group |
BEFREE |
Attributable to epigenetic DNA methylation, ASS1 deficiency may link to the therapeutic sensitivity to the arginine-depriving agents and promote tumor aggressiveness through its newly identified tumor suppressor function.
|
23897555 |
2014 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1.
|
24285724 |
2014 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%).
|
25121552 |
2014 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In addition to delayed wound closure and fewer invading cells in a Matrigel assay, ASS1 reexpression reduced tumor cell proliferation, induced G1-phase arrest, and downregulated cyclin E with corresponding growth inhibition in soft agar and xenograft assays.
|
23549872 |
2013 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Based on these results, the assessment of ASS expression in malignant mesothelioma tissues may allow the identification of subgroups of tumors with an increased sensitivity to the toxic effects of this drug.
|
22074703 |
2012 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression.
|
18473854 |
2008 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Thus far, an arginine-depleting enzyme for killing ASS-positive tumors has not been reported.
|
17210712 |
2007 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
These data indicate that sensitivity of melanoma and HCC is due to the absence of argininosuccinate synthetase in these cells and that an effective formulation of ADI, which causes a sustained decrease in arginine, may be a useful treatment for arginine auxotrophic tumors including melanoma and HCC.
|
12359751 |
2002 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13).Only two tumours had LOH on 9q.
|
8208343 |
1994 |