scholarly journals Roles of Nrf2 in Gastric Cancer: Targeting for Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3157
Author(s):  
Tahereh Farkhondeh ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Mohsen Azimi-Nezhad ◽  
Fatemeh Forouzanfar ◽  
Aranka Brockmueller ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Redox Balance ◽  
Related Factor ◽  
Clinical Prognosis ◽  
Beneficial Effects ◽  
Tumor Research ◽  
Antioxidant Gene Expression ◽  
Nrf2 Expression

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a specific transcription factor with potent effects on the regulation of antioxidant gene expression that modulates cell hemostasis under various conditions in tissues. However, the effects of Nrf2 on gastric cancer (GC) are not fully elucidated and understood. Evidence suggests that uncontrolled Nrf2 expression and activation has been observed more frequently in malignant tumors, including GC cells, which is then associated with increased antioxidant capacity, chemoresistance, and poor clinical prognosis. Moreover, Nrf2 inhibitors and the associated modulation of tumor cell redox balance have shown that Nrf2 also has beneficial effects on the therapy of various cancers, including GC. Based on previous findings on the important role of Nrf2 in GC therapy, it is of great interest to scientists in basic and clinical tumor research that Nrf2 can be active as both an oncogene and a tumor suppressor depending on different background situations.

scholarly journals Detection of Circulating Tumor Cells and Its Application in Prostate Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 3-7
Author(s):  
Jin-Qi Song ◽  
Ya-Nan Zhou ◽  
Gang-Liang Tu ◽  
Chang-Li Xu ◽  
Hui Xu
Keyword(s):  
Prostate Cancer ◽  
Early Diagnosis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Malignant Tumors ◽  
Depth Study ◽  
Tumor Research ◽  
The Common ◽  
Development And Evolution

In recent years, circulating tumor cells have become the focus of tumor research. In-depth study of the role of circulating tumor cells in the genesis, development, and evolution of tumors will be of great significance for the early detection, early diagnosis, early treatment, and prognosis of tumors. Prostate cancer is one of the common male malignant tumors, and the role of circulating tumor cells in prostate cancer has been increasing year by year. This article will focus on the progress of circulating tumor cells detection and its application in prostate cancer.

scholarly journals Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Yota Kawasaki ◽  
Sumiya Ishigami ◽  
Takaaki Arigami ◽  
Yoshikazu Uenosono ◽  
Shigehiro Yanagita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Related Factor ◽  
Nuclear Factor ◽  
Clinicopathological Significance ◽  
Nrf2 Expression

Cytokine status in the omentum and peritoneum in metastatic gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16557-e16557
Author(s):  
Elena Yu. Zlatnik ◽  
Oleg I. Kit ◽  
Aleksandr B. Sagakyants ◽  
Ekaterina I. Zolotareva ◽  
Oksana G. Shulgina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Metastatic Gastric Cancer ◽  
Greater Omentum ◽  
Specific Content ◽  
Secondary Tumor ◽  
Tnf Α ◽  
Biuret Method ◽  
The Mean

e16557 Background: Gastric cancer (GC) is one of the most common malignant tumors and the second most common cause of cancer deaths in Russia. Many researchers note the ambiguous role of cytokines in the pathogenesis of tumor processes. The purpose of the study was to determine characteristics of the cytokine status in the omentum and peritoneum of patients with metastatic GC. Methods: The main group (Mgr) included 23 patients with T2-4N0-3M1 GC with metastases to the peritoneum and greater omentum, the mean age 58.9±9.7 years. The comparison group (Cgr) included 20 non-cancer patients, the mean age 55.9±9.7 years. Tissues of the omentum (OT) and peritoneum (PT) were obtained from all patients during cytoreductive and diagnostic surgeries. Ex tempore tissues were disintegrated using BD Medimachine (USA) with 0.9% NaCl; the cell suspension was centrifuged, and the supernatant was collected and aliquoted. Levels of cytokines IL-1β, IL-2, IL-6, IL-8, IL-18, TNF-α, IL-10 (Vektor-Best, Russia) and IL-1RA (eBioscience, Austria) were determined by ELISA. The results were expressed as the specific content per 1 g of protein evaluated by the biuret method (pg/mL/g of protein). Statisical analysis of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Significance of differences was evaluated using the Mann-Whitney and Wilkinson tests; differences were considered significant at p < 0.05. Results: In Cgr, levels of IL-6, IL-8, IL-18 and IL-1β in OT were 4.1±1.1, 3.4±0.7, 21.2±5.5 and 10.8±2.1, while in Mgr – 55.3±24.4, 32.5±13.8, 144.9±48.4 and 21.01±5.4 pg/mL/g of protein, i.e. 13.7, 9.5, 6.9 and 1.9 times (p≤0.05) higher than in Cgr, respectively. The specific content of IL-1RA in OT was 12.6 times higher, p≤0.05 (215.7±69.8 vs. 2723.1±730.1), and the IL-10 concentration did not differ significantly. In PT of Cgr, levels of IL-8, IL-18 and IL-6 were 9.8±7.3, 35.2±21.7, 7.5±3.7, and in Mgr – 250.7±21.4, 322.9±16.9, 61.1±27.6 pg/mL/g, i.e. 25.7, 9.2 and 8.2 times (p≤0.05) higher than in Cgr. IL-1RA in PT of Mgr was 24.4 times higher than in Cgr, p≤0.05 (7656.2±3160.3 vs. 357.69±180.86). Conclusions: A certain microenvironment is formed in OT and PT affected by metastases, with specific features in the ratio and concentrations of various cytokines, which undoubtedly contribute to the formation of a secondary tumor.

scholarly journals Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 758
Author(s):  
Kyung-Soo Chun ◽  
Do-Hee Kim ◽  
Young-Joon Surh
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Therapy Resistance ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cellular Redox ◽  
Reductive Stress

Redox homeostasis is not only essential for the maintenance of normal physiological functions, but also plays an important role in the growth, survival, and therapy resistance of cancer cells. Altered redox balance and consequent disruption of redox signaling are implicated in the proliferation and progression of cancer cells and their resistance to chemo- and radiotherapy. The nuclear factor erythroid 2 p45-related factor (Nrf2) is the principal stress-responsive transcription factor that plays a pivotal role in maintaining cellular redox homeostasis. Aberrant Nrf2 overactivation has been observed in many cancerous and transformed cells. Uncontrolled amplification of Nrf2-mediated antioxidant signaling results in reductive stress. Some metabolic pathways altered due to reductive stress have been identified as major contributors to tumorigenesis. This review highlights the multifaceted role of reductive stress in cancer development and progression.

scholarly journals XAGE-1b Promotes the Proliferation, Invasion and Metastasis of Gastric Cancer

2020 ◽  
Author(s):  
Hui Men ◽  
Zhi-wei Zhang ◽  
Gui-feng Lu ◽  
Shun Tan ◽  
Wen-Hui Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Survival Curve ◽  
Biological Marker ◽  
Invasion And Metastasis ◽  
Treatment Target ◽  
Kaplan Meier ◽  
Proliferation And Invasion

Abstract Background X antigen family member 1B (XAGE-1b), a member of XAGE subfamily and GAGE family, is upregulated in some malignant tumors and has been associated with the proliferation, invasion and metastasis of tumors. However, the biological roles of XAGE-1b in gastric cancer (GC) still remain unclear. Methods We detected the expression of XAGE-1b in 60 paired fresh tissues of GC patients by real-time RT-PCR. Kaplan-Meier survival curve was explored to analyze 5-year survival time of GC patients. Function experiments were performed to estimate the role of XAGE-1b on the proliferation, invasion and metastasis of GC cells. Informatic analysis was applied to investigate the potential mechanisms. Results XAGE-1b was obviously upregulated in GC tissues. XAGE-1b was correlated significantly with poor prognosis of GC patients. XAGE-1b markedly promoted the proliferation and invasion in GC cell lines in vitro. Knockdown of XAGE-1b promoted the pulmonary metastatic ability in nude mice. Moreover, XAGE-1b was positively or negatively correlated with the expression of CLDN6 and CHGA, which regulated the progression of GC. Conclusions XAGE-1b could act as an oncogene in GC, which provides a potential biological marker or treatment target for GC.

scholarly journals Duodenogastric refluх: a look at the problem in terms of carcinogenesis

2019 ◽  
pp. 108-111
Author(s):  
Z. M. Galeeva ◽  
R. G. Toukhbatullina ◽  
A. I. Gaisina
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Duodenogastric Reflux ◽  
Malignant Degeneration ◽  
Chain Reaction ◽  
Biliary Reflux ◽  
Polymerase Chain ◽  
Detailed Diagnosis ◽  
Conjugated Bile Acids

The role of duodenogastric reflux (DGR) in malignant degeneration of the gastric mucosa. It was demonstrated by immunohistochemistry using monoclonal antibodies to p53, PCNA, CD10, MUC2, MUC5AC, MUC6, CD31 and the polymerase chain reaction to detect CDX1, CDX2, FXR genes. The main carcinogenic components of bile are lysolecithin and conjugated bile acids. Biliary reflux increases the risk of malignant tumors in combination with Helicobacter pylori. DGR is one of the etiological factors for gastric cancer, so it determines the necessity for detailed diagnosis in clinical practice.

scholarly journals Bromodomain and Extraterminal (BET) Protein Inhibition Restores Redox Balance and Inhibits Myofibroblast Activation

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Carmel J. W. Stock ◽  
Charalambos Michaeloudes ◽  
Patricia Leoni ◽  
Andrew L. Durham ◽  
Sharon Mumby ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Critical Role ◽  
Redox Balance ◽  
Protein Isoforms ◽  
Related Factor ◽  
Myofibroblast Differentiation ◽  
Ros Production ◽  
Bet Protein

Background and Objective. Progressive pulmonary fibrosis is the main cause of death in patients with systemic sclerosis (SSc) with interstitial lung disease (ILD) and in those with idiopathic pulmonary fibrosis (IPF). Transforming growth factor-β (TGF-β) and NADPH oxidase- (NOX-) derived reactive oxygen species (ROS) are drivers of lung fibrosis. We aimed to determine the role of the epigenetic readers, bromodomain and extraterminal (BET) proteins in the regulation of redox balance in activated myofibroblasts. Methods. In TGF-β-stimulated fibroblasts, we investigated the effect of the BET inhibitor JQ1 on the mRNA expression of the prooxidant gene NOX4 and the antioxidant gene superoxide dismutase (SOD2) by quantitative RT-PCR, the antioxidant transcription factor NF-E2-related factor 2 (Nrf2) activity by a reporter assay, and intracellular ROS levels by dichlorofluorescein staining. Myofibroblast activation was determined by α-smooth muscle actin immunocytochemistry. The role of specific BET protein isoforms in NOX4 gene regulation was studied by siRNA silencing and chromatin-immunoprecipitation. Results and Conclusions. Affymetrix gene array analysis revealed increased NOX4 and reduced SOD2 expression in SSc and IPF fibroblasts. SOD2 silencing in non-ILD control fibroblasts induced a profibrotic phenotype. TGF-β increased NOX4 and inhibited SOD2 expression, while increasing ROS production and myofibroblast differentiation. JQ1 reversed the TGF-β-mediated NOX4/SOD2 imbalance and Nrf2 inactivation and attenuated ROS production and myofibroblast differentiation. The BET proteins Brd3 and Brd4 were shown to bind to the NOX4 promoter and drive TGF-β-induced NOX4 expression. Our data indicate a critical role of BET proteins in promoting redox imbalance and pulmonary myofibroblast activation and support BET bromodomain inhibitors as a potential therapy for fibrotic lung disease.

scholarly journals The role of DOT1L in the proliferation and prognosis of gastric cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Zaozhi Song ◽  
Zhuoli Wei ◽  
Qingkang Wang ◽  
Xinxin Zhang ◽  
Xiaoying Tao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Malignant Tumors ◽  
Medical Intervention ◽  
Tnm Staging ◽  
Cell Counting ◽  
Normal Tissues

Abstract Background: Disruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples. Methods: Immunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model. Results: The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo. Conclusions: This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC.

scholarly journals Emerging Perspective: Role of Increased ROS and Redox Imbalance in Skin Carcinogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Dehai Xian ◽  
Rui Lai ◽  
Jing Song ◽  
Xia Xiong ◽  
Jianqiao Zhong
Keyword(s):  
Skin Cancer ◽  
Malignant Tumors ◽  
Cell Metabolism ◽  
Redox Balance ◽  
Skin Carcinogenesis ◽  
Toxic Dose ◽  
Redox Imbalance ◽  
Related Data ◽  
Cancer Management

Strategies to battle malignant tumors have always been a dynamic research endeavour. Although various vehicles (e.g., chemotherapeutic therapy, radiotherapy, surgical resection, etc.) are used for skin cancer management, they mostly remain unsatisfactory due to the complex mechanism of carcinogenesis. Increasing evidence indicates that redox imbalance and aberrant reactive oxygen species (ROS) are closely implicated in the oncogenesis of skin cancer. When ROS production goes beyond their clearance, excessive or accumulated ROS could disrupt redox balance, induce oxidative stress, and activate the altered ROS signals. These would damage cellular DNA, proteins, and lipids, further leading to gene mutation, cell hyperproliferation, and fatal lesions in cells that contribute to carcinogenesis in the skin. It has been known that ROS-mediated skin carcinogenesis involves multiple ways, including modulating related signaling pathways, changing cell metabolism, and causing the instability of the genome and epigenome. Nevertheless, the exact role of ROS in skin cancer has not been thoroughly elucidated. In spite of ROS inducing skin carcinogenesis, toxic-dose ROS could trigger cell death/apoptosis and, therefore, may be an efficient therapeutic tool to battle skin cancer. Considering the dual role of ROS in the carcinogenesis and treatment of skin cancer, it would be essential to clarify the relationship between ROS and skin cancer. Thus, in this review, we get the related data together to seek the connection between ROS and skin carcinogenesis. Besides, strategies basing on ROS to fight skin cancer are discussed.

Intracrinology and gastric cancer

2017 ◽  
Vol 86 (1) ◽  
pp. 76
Author(s):  
Bartosz Adam Frycz ◽  
Paweł Piotr Jagodziński
Keyword(s):  
Gastric Cancer ◽  
Steroid Hormones ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Short Review ◽  
Therapeutic Approaches ◽  
Peripheral Tissues ◽  
Expression Of Genes ◽  
Genes Encoding

Overall incidence of gastric cancer (GC) in most populations is approximately two times higher in men than women. Therefore, steroid hormones are suspect to play a role in gastric carcinogenesis. Large amounts of steroid hormones in postmenopausal women and older men are synthesized in peripheral tissues through enzymatic conversion of blood derived precursors into active estrogens and androgens in so called, intracrine mechanism. Moreover, abnormal expression of genes encoding steroidogenic enzymes was shown in numerous malignant tumors including GC. These abnormalities can be associated with deregulated production of steroid hormones in gastric tissue and thus affect the risk of GC. For that reason this short review aims to summarize the current knowledge about the expression of genes involved in metabolism of steroid hormones in normal and malignant gastric mucosa and thus, estimate the potential of these tissues to intracrine synthesis of steroid hormones. This findings could be useful in understanding the role of above mechanism in GC and could help to find therapeutic approaches in future.

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