ArticleInternational journal of molecular sciences2017
The Combination of Arginine Deprivation and 5-Fluorouracil Improves Therapeutic Efficacy in Argininosuccinate Synthetase Negative Hepatocellular Carcinoma.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Trial
- A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma.Investigational new drugs · 2021Trial
- The Role and Treatment Strategies of Ammonia-Related Metabolism in Tumor Microenvironment.Current gene therapy · 2025Review
- From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.Cold Spring Harbor perspectives in medicine · 2024Review
- Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected withFrontiers in immunology · 2024Article
- Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism.Cell reports. Medicine · 2022Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- [Study on the clinical significance and correlation of arginase-1 and inducible nitric oxide synthase expression in hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Article
- A novel Romani microdeletion variant in the promoter sequence ofMolecular genetics and metabolism reports · 2020Article
- Collaboration Between RSK-EphA2 and Gas6-Axl RTK Signaling in Arginine Starvation Response That Confers Resistance to EGFR Inhibitors.Translational oncology · 2020Article
- Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.Molecular cancer therapeutics · 2019Article
- mTOR signalling and cellular metabolism are mutual determinants in cancer.Nature reviews. Cancer · 2018Review
- A phase 1 study of ADI-PEG 20 and modified FOLFOX6 in patients with advanced hepatocellular carcinoma and other gastrointestinal malignancies.Cancer chemotherapy and pharmacology · 2018Article
- Argininosuccinate Synthetase-1 (ASS1) Loss in High-Grade Neuroendocrine Carcinomas of the Urinary Bladder: Implications for Targeted Therapy with ADI-PEG 20.Endocrine pathology · 2018Article
- Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI-PEG20 treatment in CCA cell lines.Oncology letters · 2018Article
- Metabolomic profiling identifies distinct phenotypes for ASS1 positive and negative GBM.BMC cancer · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Argininosuccinate synthetase (ASS), a key enzyme to synthesize arginine is down regulated in many tumors including hepatocellular carcinoma (HCC). Similar to previous reports, we have found the decrease in ASS expression in poorly differentiated HCC. These ASS(-) tumors are auxotrophic for arginine. Pegylated arginine deiminase (ADI-PEG20), which degrades arginine, has shown activity in these tumors, but the antitumor effect is not robust and hence combination treatment is needed. Herein, we have elucidated the effectiveness of ADI-PEG20 combined with 5-Fluorouracil (5-FU) in ASS(-)HCC by targeting urea cycle and pyrimidine metabolism using four HCC cell lines as model. SNU398 and SNU387 express very low levels of ASS or ASS(-) while Huh-1, and HepG2 express high ASS similar to normal cells. Our results showed that the augmented cytotoxic effect of combination treatment only occurs in SNU398 and SNU387, and not in HepG2 and Huh-1 (ASS(+)) cells, and is partly due to reduced anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP), myeloid leukemia cell differentiation protein (Mcl-1) and B-cell lymphoma-2 (Bcl-2). Importantly, lack of ASS also influences essential enzymes in pyrimidine synthesis (carbamoyl-phosphate synthetase2, aspartate transcarbamylase and dihydrooratase (CAD) and thymidylate synthase (TS)) and malate dehydrogenase-1 (MDH-1) in TCA cycle. ADI-PEG20 treatment decreased these enzymes and made them more vulnerable to 5-FU. Transfection of ASS restored these enzymes and abolished the sensitivity to ADI-PEG20 and combination treatment. Overall, our data suggest that ASS influences multiple enzymes involved in 5-FU sensitivity. Combining ADI-PEG20 and 5-FU may be effective to treat ASS(-)hepatoma and warrants further clinical investigation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.