Search results for: Argininosuccinate synthetase 1
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#33859183 2021/04/15 To Up
Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.Argininosuccinate synthase (ASS1) is a ubiquitous enzyme in mammals that catalyzes the formation of argininosuccinate from citrulline and aspartate. ASS1 genetic deficiency in patients leads to an autosomal recessive urea cycle disorder citrullinemia, while its somatic silence or down-regulation is very common in various human cancers. Here, we show that ASS1 functions as a tumor suppressor in breast cancer, and the pesticide spinosyn A (SPA) and its derivative LM-2I suppress breast tumor cell proliferation and growth by binding to and activating ASS1. The C13-C14 double bond in SPA and LM-2I while the Cys97 (C97) site in ASS1 are critical for the interaction between ASS1 and SPA or LM-2I. SPA and LM-2I treatment results in significant enhancement of ASS1 enzymatic activity in breast cancer cells, particularly in those cancer cells with low ASS1 expression, leading to reduced pyrimidine synthesis and consequently the inhibition of cancer cell proliferation. Thus, our results establish spinosyn A and its derivative LM-2I as potent ASS1 enzymatic activator and tumor inhibitor, which provides a therapeutic avenue for tumors with low ASS1 expression and for those non-tumor diseases caused by down-regulation of ASS1.
Zizheng Zou, Xiyuan Hu, Tiao Luo, Zhengnan Ming, Xiaodan Chen, Li Xia, Wensong Luo, Jijia Li, Na Xu, Ling Chen, Dongsheng Cao, Min Wen, Fanrong Kong, Kunjian Peng, Yuanzhu Xie, Xuan Li, Dayou Ma, Chuanyu Yang, Ceshi Chen, Wenjun Yi, Ousheng Liu, Suyou Liu, Junli Luo, Zhiyong Luo
1242 related Products with: Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.1000 TESTS/0.65ml10 mg1 mg50 ug 20 96 wells (1 kit)1 kit(96 Wells)1 kit(96 Wells)100ul25 mg
#33856599 2021/04/15 To Up
A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma.Pegylated recombinant human arginase (PEG-BCT-100) is an arginine depleting drug. Preclinical studies showed that HCC is reliant on exogenous arginine for growth due to the under-expression of the arginine regenerating enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC).
Stephen L Chan, Paul N M Cheng, Angela M Liu, Landon L Chan, Leung Li, Cheuk M Chu, Charing C N Chong, Yat M Lau, Winnie Yeo, Kelvin K C Ng, Simon C H Yu, Tony S K Mok, Anthony W H Chan
2901 related Products with: A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma.100ul
#33851512 2021/04/13 To Up
Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to hyperammonemia with variable clinical manifestations. Using data from a nationwide study, we investigated the onset time, gene variants, clinical manifestations, and treatment of patients with UCDs in Japan. Of the 229 patients with UCDs diagnosed and/or treated between January 2000 and March 2018, identified gene variants and clinical information were available for 102 patients, including 62 patients with ornithine transcarbamylase (OTC) deficiency, 18 patients with carbamoyl phosphate synthetase 1 (CPS1) deficiency, 16 patients with argininosuccinate synthetase (ASS) deficiency, and 6 patients with argininosuccinate lyase (ASL) deficiency. A total of 13, 10, 4, and 5 variants in the OTC, CPS1, ASS, and ASL genes were respectively identified as novel variants, which were neither registered in ClinVar databases nor previously reported. The onset time and severity in patients with UCD could be predicted based on the identified gene variants in each patient from this nationwide study and previous studies. This genetic information may help in predicting the long-term outcome and determining specific treatment strategies such as liver transplantation in patients with UCDs.
Jun Kido, Shirou Matsumoto, Keishin Sugawara, Takaaki Sawada, Kimitoshi Nakamura
2816 related Products with: Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review.2 Pieces/Box2 Pieces/Box2 Pieces/Box100ug1 Set1 Set2 Pieces/Box1 Set1 Set
#33840128 2021/04/11 To Up
Long-term outcome of urea cycle disorders: Report from a nationwide study in Japan.Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20 years of age of male and female patients with late-onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (P < .001 and P = .028, respectively). Hemodialysis and liver transplantation did not prevent poor neurodevelopmental outcomes. While treatment including medication, hemodialysis, and liver transplantation may aid in decreasing blood ammonia and/or preventing severe hyperammonemia, a blood ammonia level ≥ 360 μmol/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion, although current therapy for UCDs has advanced and helped saving lives, patients with blood ammonia levels ≥ 360 μmol/L at onset often have impaired neurodevelopmental outcomes. Novel neuroprotective measures should therefore be developed to achieve better neurodevelopmental outcomes in these patients.
Jun Kido, Shirou Matsumoto, Johannes Häberle, Yoko Nakajima, Yoichi Wada, Narutaka Mochizuki, Kei Murayama, Tomoko Lee, Hiroshi Mochizuki, Yoriko Watanabe, Reiko Horikawa, Mureo Kasahara, Kimitoshi Nakamura
2245 related Products with: Long-term outcome of urea cycle disorders: Report from a nationwide study in Japan.100 μg 0.1 mg 100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg
#33838671 2021/04/10 To Up
Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma.Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids.
Sanghwa Kim, Minji Lee, Yeonhwa Song, Su-Yeon Lee, Inhee Choi, I-Seul Park, Jiho Kim, Jin-Sun Kim, Kang Mo Kim, Haeng Ran Seo
2351 related Products with: Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma.100μg100ug100ug100μg100uL
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#33664852 2021/01/25 To Up
Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy.Arginine synthesis deficiency due to the suppressed expression of ASS1 (argininosuccinate synthetase 1) represents one of the most frequently occurring metabolic defects of tumor cells. Arginine-deprivation therapy has gained increasing attention in recent years. One challenge of ADI-PEG20 (pegylated ADI) therapy is the development of drug resistance caused by restoration of ASS1 expression and other factors. The goal of this work is to identify novel factors conferring therapy resistance. Multiple, independently derived ADI-resistant clones including derivatives of breast (MDA-MB-231 and BT-549) and prostate (PC3, CWR22Rv1, and DU145) cancer cells were developed. RNA-seq and RT-PCR were used to identify genes upregulated in the resistant clones. Unbiased genome-wide CRISPR/Cas9 knockout screening was used to identify genes whose absence confers sensitivity to these cells. shRNA and CRISPR/Cas9 knockout as well as overexpression approaches were used to validate the functions of the resistant genes both and in xenograft models. The signal pathways were verified by western blotting and cytokine release. Based on unbiased CRISPR/Cas9 knockout screening and RNA-seq analyses of independently derived ADI-resistant (ADIR) clones, aberrant activation of the TREM1/CCL2 axis in addition to ASS1 expression was consistently identified as the resistant factors. Unlike ADIR, MDA-MB-231 overexpressing ASS1 cells achieved only moderate ADI resistance both and , and overexpression of ASS1 alone does not activate the TREM1/CCL2 axis. These data suggested that upregulation of TREM1 is an independent factor in the development of strong resistance, which is accompanied by activation of the AKT/mTOR/STAT3/CCL2 pathway and contributes to cell survival and overcoming the tumor suppressive effects of ASS1 overexpression. Importantly, knockdown of TREM1 or CCL2 significantly sensitized ADIR toward ADI. Similar results were obtained in BT-549 breast cancer cell line as well as castration-resistant prostate cancer cells. The present study sheds light on the detailed mechanisms of resistance to arginine-deprivation therapy and uncovers novel targets to overcome resistance. We uncovered TREM1/CCL2 activation, in addition to restored ASS1 expression, as a key pathway involved in full ADI-resistance in breast and prostate cancer models.
Cheng-Ying Chu, Yi-Ching Lee, Cheng-Han Hsieh, Chi-Tai Yeh, Tsu-Yi Chao, Po-Hung Chen, I-Hsuan Lin, Tsung-Han Hsieh, Jing-Wen Shih, Chia-Hsiung Cheng, Che-Chang Chang, Ping-Sheng Lin, Yuan-Li Huang, Tsung-Ming Chen, Yun Yen, David K Ann, Hsing-Jien Kung
2212 related Products with: Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy.25 G 25 G1 ml1 mg 5 G1 module100ug1 ml40 assays100 μg25 g
#33614409 2021/02/07 To Up
Physical, cognitive, and social status of patients with urea cycle disorders in Japan.Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to hyperammonemia. Severe hyperammonemia adversely affects the brain. Therefore, we conducted a nationwide study between January 2000 and March 2018 to understand the present status of UCD patients in Japan regarding diagnosis, treatments, and outcomes. A total of 229 patients with UCDs (126 patients: ornithine transcarbamylase deficiency [OTCD]; 33: carbamoyl phosphate synthetase 1 deficiency [CPS1D]; 48: argininosuccinate synthetase deficiency [ASSD]; 14: argininosuccinate lyase deficiency [ASLD]; and 8: arginase 1 deficiency [ARG1D]) were enrolled in the present study. Although growth impairment is common in patients with UCDs, we discovered that Japanese patients with UCDs were only slightly shorter than the mean height of the general adult population in Japan. Patients with neonatal-onset UCDs are more likely to experience difficulty finding employment and a spouse; however, some patients with late-onset UCDs were employed and married. Additionally, intellectual and developmental disabilities, such as attention deficit hyperactivity disorder (ADHD) and autism, hinder patients with UCDs from achieving a healthy social life. Moreover, we identified that it is vital for patients with UCDs presenting with mild to moderate intellectual disabilities to receive social support. Therefore, we believe the more robust social support system for patients with UCDs may enable them to actively participate in society.
Jun Kido, Shirou Matsumoto, Tetsuya Ito, Shinichi Hirose, Kaori Fukui, Kanako Kojima-Ishii, Yuichi Mushimoto, Shinobu Yoshida, Mika Ishige, Norio Sakai, Kimitoshi Nakamura
2832 related Products with: Physical, cognitive, and social status of patients with urea cycle disorders in Japan.2 Pieces/Box2 Pieces/Box2 Pieces/Box1 Set1 Set2 Pieces/Box1 Set1 Set
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