Article
Biochemistry & Molecular Biology
Julian Peter Mueller, Dirk Gruendemann
Summary: In this study, it has been demonstrated that the ergothioneine transporter ETT does not transport nucleosides but efficiently transports gemcitabine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Sheron Perera, Gun Ho Jang, Yifan Wang, Deirdre Kelly, Michael Allen, Amy Zhang, Robert E. Denroche, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, Ravi Ramjeesingh, James Biagi, Bernard Lam, Julie Wilson, Sandra E. Fischer, George Zogopoulos, Faiyaz Notta, Steven Gallinger, Robert C. Grant, Jennifer J. Knox, Grainne M. O'Kane
Summary: In advanced PDAC, hENT1 mRNA expression predicts ORR and OS in patients receiving GnP, while no association was observed in patients receiving mFFX.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sheng-Lan Shi, Hiroyuki Fukuda, Takeshi Chujo, Takahisa Kouwaki, Hiroyuki Oshiumi, Kazuhito Tomizawa, Fan-Yan Wei
Summary: This study revealed that RNA-derived modified nucleosides are transported to extracellular space through equilibrative nucleoside transporters 1 and 2, with elevated levels of intracellular modified nucleosides being associated with an induction of autophagy response. Defective export of these modified nucleosides can lead to profound consequences for pathophysiology, as indicated by their role in inducing autophagy response and promoting Zika virus replication.
Article
Neurosciences
Ching-Ya Chen, Fang-Yi Chou, Ya-Gin Chang, Chin-Jui Ho, Kuo-Chen Wu, Chia-Lin Hsu, Yijuang Chern, Chun-Jung Lin
Summary: This study investigated the impact of ENT2 deletion on Huntington's disease using a mouse model. The results showed that ENT2 deletion worsened motor dysfunction and increased the accumulation of mutant huntingtin in the striatum of R6/2 mice. Furthermore, ENT2 deletion disrupted energy metabolism, leading to decreased ATP levels and increased AMP/ATP ratio, as well as activation of AMPK and impaired mitochondrial respiration.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Kuan-Yu Chen, Chiao-Shin Lu, Cheng-Yoong Pang, Chin-Jui Ho, Kuo-Chen Wu, Hsiu-Wei Yang, Hsin-Lin Lai, Yijuang Chern, Chun-Jung Lin
Summary: This study demonstrated the important role of equilibrative nucleoside transporter 1 (Ent1) in the inflammatory responses and functional recovery of spinal cord injury (SCI). Genetic deletion or pharmacological inhibition of Ent1 reduced neuroinflammation, improved neurological function and gait, reduced lesion size, and protected neurons in mice with SCI.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jessica C. Boakes, Steven. P. D. Harborne, Jessie T. S. Ngo, Christos Pliotas, Adrian Goldman
Summary: Human equilibrative nucleoside transporters are important targets for cardiovascular, cancer, and viral therapies. This study identified variants of human equilibrative nucleoside transporter isoform 1 that stabilize different states of the transporter, providing insight into its transport mechanism and gating.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Magali Saez-Ayala, Laurent Hoffer, Sebastien Abel, Khaoula Ben Yaala, Benoit Sicard, Guillaume P. Andrieu, Mehdi Latiri, Emma K. Davison, Marco A. Ciufolini, Paul Bremond, Etienne Rebuffet, Philippe Roche, Carine Derviaux, Edwige Voisset, Camille Montersino, Remy Castellano, Yves Collette, Vahid Asnafi, Stephane Betzi, Patrice Dubreuil, Sebastien Combes, Xavier Morelli
Summary: Cancer cells rely on two pathways, the de novo pathway and the salvage pathway, for nucleotide synthesis. In this study, we developed a potent inhibitor for the salvage pathway by using a multidisciplinary approach combining computational design and experimental evaluations. Our lead compound, OR0642, showed significantly higher potency compared to the original compound, masitinib, identified through drug repositioning. In a xenograft mouse model of T-cell acute lymphoblastic leukemia, OR0642 in combination with a physiological inhibitor of the de novo pathway doubled the survival rate, demonstrating the proof-of-concept of this drug design strategy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Prince J. Salvador, Heather B. Jacobs, Lujain Alnouri, Asia Fee, Lynn M. Utley, Madison Mabry, Hannah Krajeck, Christopher Dicksion, Ahmed M. Awad
Summary: A convenient synthesis method for six nucleoside analogues modified with benzenesulfonamide derivatives was reported. The molecular docking experiments showed that these analogues, enhanced with electron-withdrawing groups, have potential as ribonucleotide reductase inhibitors with favorable pharmacological and toxicity profiles.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Cell Biology
Liyuan Wu, Le Yin, Linxiang Ma, Jiarui Yang, Feiya Yang, Baofa Sun, Xing Nianzeng
Summary: High expression of RRM2 is associated with tumor prognosis and immunotherapy. The study reveals that high levels of RRM2 are associated with worse patient survival and immunotherapy effects through pan-cancer analysis and risk score analysis.
Article
Medicine, General & Internal
Jung Won Chun, Boyoung Lee, Weon Seo Park, Nayoung Han, Eun Kyung Hong, Eun Young Park, Sung Sik Han, Sang-Jae Park, Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo
Summary: The study aimed to investigate the predictive and prognostic values of several biomarkers in patients with advanced biliary tract cancer treated with gemcitabine plus cisplatin. The results showed that increased intratumoral expression of RRM1 may predict poor survival in patients with this chemotherapy regimen.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Yang Gao, Bin Chen, Ruru Wang, An Xu, Lijun Wu, Huayi Lu, Guoping Zhao
Summary: Targeting RRM1 promotes ferroptosis and affects the sensitivity of cancer cells to radiation and chemotherapy. RRM1 disrupts the activity and expression of antioxidant enzyme GPX4, leading to increased accumulation of reactive oxygen species and lipid peroxidation. Furthermore, targeting RRM1 also increases radiation-induced DNA damage and apoptotic signaling, causing crosstalk between ferroptosis and apoptosis.
CELL DEATH DISCOVERY
(2022)
Article
Immunology
Kuo-Chen Wu, Chih-Yu Lee, Yijuang Chern, Chun-Jung Lin
Summary: The study suggests that deleting the ENT2 gene can alleviate LPS-induced neuroinflammation and blood-brain barrier breakdown, as well as improve cognitive functions such as spatial memory and hippocampal long-term potentiation. Further experiments revealed that neuronal survival was preserved in Ent2 KO mice, while WT mice exhibited synaptic and neuronal damage.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Hematology
Berengere Koehl, Livia Claude, Karen Reminy, Vanessa Tarer, Veronique Baccini, Marc Romana, Yves Colin-Aronovicz, Vijaya L. Damaraju, Michael Sawyer, Thierry Peyrard, Maryse Etienne-Julan, Caroline Le Van Kim, Slim Azouzi, Luc Reininger
Summary: This study investigated the expression of erythrocyte ENT1 in adult patients with sickle cell disease (SCD) and carriers of sickle cell trait (SCT). The results showed that the expression levels of erythrocyte ENT1 were not significantly different from normal controls in patients with SCD in steady state conditions. However, the expression of erythrocyte ENT1 was significantly decreased in SCD patients during painful vaso-occlusive episodes and in healthy SCT carriers.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Taiki Yamamura, Katsuya Narumi, Tsukika Ohata, Hiroshi Satoh, Takao Mori, Ayako Furugen, Masaki Kobayashi, Ken Iseki
Summary: This study investigated the role of human concentrative nucleoside transporters (CNTs) in transporting deoxyribonucleosides (dNs) along with ribonucleosides. The results showed that CNTs can transport dNs, with CNT1 and CNT2 selectively transporting pyrimidine and purine dNs respectively, and CNT3 transporting both types of dNs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Junlei Han, Jianping Hu, Fang Sun, Hongzhi Bian, Bingxiang Tang, Xiang Fang
Summary: miR-20a suppresses NSCLC growth by inhibiting the RRM2-mediated PI3K/Akt signaling pathway, serving as a potential tumor suppressor and molecular target for NSCLC treatment.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)