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Article ; Online: Glutamine synthetase: a tumor suppressor in hepatocellular carcinoma?

Dai, Weiwei / Zong, Wei-Xing

2023 Volume 15, Issue 1

MeSH term(s)	Humans ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Glutamate-Ammonia Ligase/genetics ; Genes, Tumor Suppressor
Chemical Substances	Glutamate-Ammonia Ligase (EC 6.3.1.2)
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2500949-7
ISSN	1759-4685 ; 1759-4685
ISSN (online)	1759-4685
ISSN	1759-4685
DOI	10.1093/jmcb/mjad007
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Article ; Online: Endocrine-disrupting compounds and metabolomic reprogramming in breast cancer.

Winz, Cassandra / Zong, Wei-Xing / Suh, Nanjoo

Journal of biochemical and molecular toxicology

2023 Volume 37, Issue 12, Page(s) e23506

Abstract: Endocrine-disrupting chemicals pose a growing threat to human health through their increasing presence in the environment and their potential interactions with the mammalian endocrine systems. Due to their structural similarity to hormones like estrogen, ...

Abstract	Endocrine-disrupting chemicals pose a growing threat to human health through their increasing presence in the environment and their potential interactions with the mammalian endocrine systems. Due to their structural similarity to hormones like estrogen, these chemicals can interfere with endocrine signaling, leading to many deleterious effects. Exposure to estrogenic endocrine-disrupting compounds (EDC) is a suggested risk factor for the development of breast cancer, one of the most frequently diagnosed cancers in women. However, the mechanisms through which EDCs contribute to breast cancer development remain elusive. To rapidly proliferate, cancer cells undertake distinct metabolic programs to utilize existing nutrients in the tumor microenvironment and synthesize macromolecules de novo. EDCs are known to dysregulate cell signaling pathways related to cellular metabolism, which may be an important mechanism through which they exert their cancer-promoting effects. These altered pathways can be studied via metabolomic analysis, a new advancement in -omics technologies that can interrogate molecular pathways that favor cancer development and progression. This review will summarize recent discoveries regarding EDCs and the metabolic reprogramming that they may induce to facilitate the development of breast cancer.
MeSH term(s)	Animals ; Humans ; Female ; Breast Neoplasms/chemically induced ; Estrogens ; Signal Transduction ; Risk Factors ; Endocrine Disruptors/toxicity ; Mammals ; Tumor Microenvironment
Chemical Substances	Estrogens ; Endocrine Disruptors
Language	English
Publishing date	2023-08-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1410020-4
ISSN	1099-0461 ; 1095-6670
ISSN (online)	1099-0461
ISSN	1095-6670
DOI	10.1002/jbt.23506
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Article ; Online: The role of ferroptosis in cardio-oncology.

Hou, Kai / Liu, Lin / Fang, Zhi-Hui / Zong, Wei-Xing / Sun, Daqiang / Guo, Zhigang / Cao, Lu

Archives of toxicology

2024 Volume 98, Issue 3, Page(s) 709–734

Abstract: With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor ... ...

Abstract	With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology" has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both cardiovascular and neoplastic diseases. The balance between intracellular oxidative stress and antioxidant defense is crucial in regulating ferroptosis. Tumor cells can evade ferroptosis by upregulating multiple antioxidant defense pathways, while many antitumor therapies rely on downregulating antioxidant defense and promoting ferroptosis in cancer cells. Unfortunately, these ferroptosis-inducing antitumor therapies often lack tissue specificity and can also cause injury to the heart, resulting in ferroptosis-induced cardiotoxicity. A range of cardioprotective agents exert cardioprotective effects by inhibiting ferroptosis. However, these cardioprotective agents might diminish the efficacy of antitumor treatment due to their antiferroptotic effects. Most current research on ferroptosis only focuses on either tumor treatment or heart protection but rarely considers both in concert. Therefore, further research is needed to study how to protect the heart during antitumor therapies by regulating ferroptosis. In this review, we summarized the role of ferroptosis in the treatment of neoplastic diseases and cardiovascular diseases and also attempted to propose further research directions for ferroptosis in the field of cardio-oncology.
MeSH term(s)	Humans ; Antioxidants ; Cardio-Oncology ; Cardiotonic Agents ; Cardiotoxicity ; Cardiovascular Diseases/chemically induced ; Ferroptosis
Chemical Substances	Antioxidants ; Cardiotonic Agents
Language	English
Publishing date	2024-01-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03665-3
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Article: [Dilemma and breakthrough of acupuncture-moxibustion department under the situation of rapid expansion of hospital].

Chen, Shao-Zong / Pan, Wei-Xing / Jing, Xiang-Hong / Fang, Jian-Qiao

Zhongguo zhen jiu = Chinese acupuncture & moxibustion

2022 Volume 42, Issue 1, Page(s) 8–12

Abstract: Under the situation of the rapid expansion of hospital, the dilemma of acupuncture-moxibustion department, as well as the relevant solutions are explored. The main reasons for the shrinking situation of the service in acupuncture-moxibustion department ... ...

Abstract	Under the situation of the rapid expansion of hospital, the dilemma of acupuncture-moxibustion department, as well as the relevant solutions are explored. The main reasons for the shrinking situation of the service in acupuncture-moxibustion department include: the disease-based department division trends to divert many diseases suitably treated in acupuncture-moxibustion department; the environment pursuing economic benefits restricts the development of acupuncture-moxibustion therapy characterized by "simple and low-cost operation". There are three important approaches for breaking through the dilemma of acupuncture and moxibustion therapy. First, modifying the traditional service mode as waiting for patients in acupuncture-moxibustion department and promoting acupuncture and moxibustion technology to be adopted in other departments rather than limited only in acupuncture-moxibustion department. Second, increasing the charges of acupuncture and moxibustion technology rationally. Third, positioning accurately the role of acupuncture and moxibustion technology in health services based on its own characteristics and advantages and promoting it in community medical institutions. All of these solutions require the guidance of supporting policies.
MeSH term(s)	Acupuncture ; Acupuncture Therapy ; Hospitals ; Humans ; Moxibustion
Language	Chinese
Publishing date	2022-01-13
Publishing country	China
Document type	Journal Article
ISSN	0255-2930
ISSN	0255-2930
DOI	10.13703/j.0255-2930.20201121-0002
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Article: [Internationalized background of developing modern acupuncture and moxibustion-on the reform of teaching material of

Chen, Shao-Zong / Pan, Wei-Xing / Jing, Xiang-Hong

Zhongguo zhen jiu = Chinese acupuncture & moxibustion

2021 Volume 41, Issue 3, Page(s) 237–241

Abstract: This paper analyzes the severe challenges posed by the localization process in the internationalization of Chinese acupuncture and moxibustion to Chinese traditional acupuncture and moxibustion, and the ways to deal with the challenges. It is believed ... ...

Abstract	This paper analyzes the severe challenges posed by the localization process in the internationalization of Chinese acupuncture and moxibustion to Chinese traditional acupuncture and moxibustion, and the ways to deal with the challenges. It is believed that the lack of deep understanding of the challenges in the process of internationalization of acupuncture and moxibustion is mainly due to the lack of knowledge structure of acupuncture and moxibustion, and the innovation of acupuncture and moxibustion teaching materials is the basis of effectively adjusting the knowledge structure. The direction of the reform of acupuncture and moxibustion teaching materials should separate the modern version of acupuncture and moxibustion that conforms to the nature of science and teach it in parallel with the traditional version of acupuncture and moxibustion. The development of modern acupuncture and moxibustion in line with the nature of science is not only an urgent need to meet the challenges of western acupuncture and moxibustion, but also an internal requirement for the development of acupuncture and moxibustion itself.
MeSH term(s)	Acupuncture ; Acupuncture Therapy ; Knowledge ; Moxibustion ; Teaching ; Teaching Materials
Language	Chinese
Publishing date	2021-04-02
Publishing country	China
Document type	Journal Article
ISSN	0255-2930
ISSN	0255-2930
DOI	10.13703/j.0255-2930.20200211-0002
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Article ; Online: TRIM21 ubiquitylates GPX4 and promotes ferroptosis to aggravate ischemia/reperfusion-induced acute kidney injury.

Sun, Xiaolin / Huang, Ning / Li, Peng / Dong, Xinyi / Yang, Jiahong / Zhang, Xuemei / Zong, Wei-Xing / Gao, Shenglan / Xin, Hong

Life sciences

2023 Volume 321, Page(s) 121608

Abstract: Aims: This study aims to verify the molecular mechanism that Tripartite motif containing 21 (TRIM21) promotes ubiquitination degradation of glutathione peroxidase 4 (GPX4) by regulating ferroptosis, and to discuss the feasibility of TRIM21 as a new ... ...

Abstract	Aims: This study aims to verify the molecular mechanism that Tripartite motif containing 21 (TRIM21) promotes ubiquitination degradation of glutathione peroxidase 4 (GPX4) by regulating ferroptosis, and to discuss the feasibility of TRIM21 as a new therapeutic target for acute kidney injury (AKI). Materials and methods: Ischemia-reperfusion (I/R)-AKI model was constructed using Trim21 Key findings: In vivo, TRIM21 is highly expressed in I/R kidney tissues. Loss of TRIM21 alleviated I/R-AKI and improved renal function. The upregulation of GPX4, a key ferroptosis regulator, and the mild mitochondrial damage suggested that loss of TRIM21 had a negative regulation of ferroptosis. In vitro, TRIM21 was highly expressed in H/R models, and overexpression of TRIM21 in HK-2 cells increased ROS production, promoted intracellular iron accumulation, and boosted cellular sensitivity to RSL3 and Erastin. Mechanistically, we confirmed that GPX4 is a substrate of TRIM21 and can be degraded by TRIM21-mediated ubiquitination, suggesting that inhibiting TRIM21 attenuates ferroptosis. A JAK2 inhibitor Fedratinib downregulated TRIM21 expression and reduced damage both in vivo and in vitro, which is correlated with the upregulation of GPX4. Significance: Our study showed that loss of TRIM21 could alleviate ferroptosis induced by I/R, revealed the mechanism of ubiquitination degradation of GPX4 by TRIM21 and suggested TRIM21 is a potential target for the treatment of AKI.
MeSH term(s)	Animals ; Mice ; Ferroptosis ; Acute Kidney Injury ; Kidney/physiology ; Reperfusion Injury ; Ischemia ; Reperfusion
Language	English
Publishing date	2023-03-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121608
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Article: Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model.

Han, Han V / Efem, Richard / Rosati, Barbara / Lu, Kevin / Maimouni, Sara / Jiang, Ya-Ping / Montoya, Valeria / Van Der Velden, Adrianus / Zong, Wei-Xing / Lin, Richard Z

bioRxiv : the preprint server for biology

2024

Abstract: Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. ... ...

Abstract	Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca-/- KPC (named αKO) cancer cells induces clonal expansion of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in αKO cells (named p-αKO) leads to immune evasion, tumor progression and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with clonally expanded CD8+ T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally expanded T cells infiltrating p-αKO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.24.550301
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Article ; Online: Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer.

Han, Xinlu / Wang, Deyu / Yang, Liao / Wang, Ning / Shen, Jianliang / Wang, Jinghan / Zhang, Lei / Chen, Li / Gao, Shenglan / Zong, Wei-Xing / Wang, Yongbo

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 13, Page(s) e2319429121

Abstract: Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine ... ...

Abstract	Polyamines are a class of small polycationic alkylamines that play essential roles in both normal and cancer cell growth. Polyamine metabolism is frequently dysregulated and considered a therapeutic target in cancer. However, targeting polyamine metabolism as monotherapy often exhibits limited efficacy, and the underlying mechanisms are incompletely understood. Here we report that activation of polyamine catabolism promotes glutamine metabolism, leading to a targetable vulnerability in lung cancer. Genetic and pharmacological activation of spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme of polyamine catabolism, enhances the conversion of glutamine to glutamate and subsequent glutathione (GSH) synthesis. This metabolic rewiring ameliorates oxidative stress to support lung cancer cell proliferation and survival. Simultaneous glutamine limitation and SAT1 activation result in ROS accumulation, growth inhibition, and cell death. Importantly, pharmacological inhibition of either one of glutamine transport, glutaminase, or GSH biosynthesis in combination with activation of polyamine catabolism synergistically suppresses lung cancer cell growth and xenograft tumor formation. Together, this study unveils a previously unappreciated functional interconnection between polyamine catabolism and glutamine metabolism and establishes cotargeting strategies as potential therapeutics in lung cancer.
MeSH term(s)	Humans ; Lung Neoplasms ; Glutamine ; Polyamines/metabolism ; Lung/metabolism ; Cell Death ; Acetyltransferases/genetics ; Acetyltransferases/metabolism ; Spermine/metabolism
Chemical Substances	Glutamine (0RH81L854J) ; Polyamines ; Acetyltransferases (EC 2.3.1.-) ; Spermine (2FZ7Y3VOQX)
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2319429121
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Article: Spectrophotometric Determination of Glutamine Synthetase Activity in Cultured Cells.

Peng, I-Chen / Bott, Alex J / Zong, Wei-Xing

Bio-protocol

2019 Volume 6, Issue 19

Abstract: Glutamine synthetase (GS), which catalyzes the conversion of glutamate and ammonia to glutamine, is widely distributed in animal tissues and cell culture lines. The importance of this enzyme is suggested by the fact that glutamine, the product of GS- ... ...

Abstract	Glutamine synthetase (GS), which catalyzes the conversion of glutamate and ammonia to glutamine, is widely distributed in animal tissues and cell culture lines. The importance of this enzyme is suggested by the fact that glutamine, the product of GS-catalyzed de novo synthesis reaction, is the most abundant free amino acid in blood (Smith and Wilmore, 1990). Glutamine is involved in many biological processes including serving as the nitrogen donor for biosynthesis, as an exchanger for the import of essential amino acids, as a means to detoxifying intracellular ammonia and glutamate, and as a bioenergetics nutrient to fuel the tricarboxylic acid (TCA) cycle (Bott
Language	English
Publishing date	2019-08-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.1959
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Article: The Pleiotropic Effects of Glutamine Metabolism in Cancer.

Bott, Alex J / Maimouni, Sara / Zong, Wei-Xing

Cancers

2019 Volume 11, Issue 6

Abstract: Metabolic programs are known to be altered in cancers arising from various tissues. Malignant transformation can alter signaling pathways related to metabolism and increase the demand for both energy and biomass for the proliferating cancerous cells. ... ...

Abstract	Metabolic programs are known to be altered in cancers arising from various tissues. Malignant transformation can alter signaling pathways related to metabolism and increase the demand for both energy and biomass for the proliferating cancerous cells. This scenario is further complexed by the crosstalk between transformed cells and the microenvironment. One of the most common metabolic alterations, which occurs in many tissues and in the context of multiple oncogenic drivers, is the increased demand for the amino acid glutamine. Many studies have attributed this increased demand for glutamine to the carbon backbone and its role in the tricarboxylic acid (TCA) cycle anaplerosis. However, an increasing number of studies are now emphasizing the importance of glutamine functioning as a proteogenic building block, a nitrogen donor and carrier, an exchanger for import of other amino acids, and a signaling molecule. Herein, we highlight the recent literature on glutamine's versatile role in cancer, with a focus on nitrogen metabolism, and therapeutic implications of glutamine metabolism in cancer.
Language	English
Publishing date	2019-06-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers11060770
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