Author Correction: Plasma activity of Thioredoxin Reductase as a Novel Biomarker in Gastric Cancer

AbstractGastric cancer (GC) is one of the leading malignancies around the world. Identification of novel and efficient biomarkers for GC diagnosis and evaluation of therapeutic efficiency could improve the therapeutic strategy in future clinical application. This study aims to evaluate the levels of plasma thioredoxin reductase (TrxR) activity in GC patients to confirm its validity and efficacy in GC diagnosis and evaluation of therapeutic efficiency. 923 cases were enrolled in the current study. In the group of GC patients before clinical intervention, plasma TrxR activity [9.09 (7.96, 10.45) U/mL] was significantly higher than in healthy controls [3.69 (2.38, 5.32) U/mL]. The threshold of TrxR activity for GC diagnosis was set at 7.34 U/mL with a sensitivity of 85.5% and a specificity of 97.9%. In GC patients after chemotherapy, plasma TrxR activity was remarkably higher in patients with progressive disease or uncontrolled condition [10.07 (8.19, 11.02) U/mL] compared with patients with complete or partial response [7.12 (6.08, 8.37) U/mL] in response to chemotherapy. TrxR activity displayed the higher efficiency to distinguish between GC patients with two distinct clinical outcomes than carcinoembryonic antigen (CEA), cancer antigen 72-4 (CA72-4) and cancer antigen 19-9 (CA19-9). Moreover, combination of TrxR, CEA, CA72-4 and CA19-9 was demonstrated to be more effective in both GC diagnosis and evaluation of therapeutic efficiency than was each biomarker individually. Together, plasma TrxR activity was identified as a novel and efficient biomarker of GC, both in diagnosis and monitoring of therapeutic efficiency in response to chemotherapy.

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EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

Oncotarget ◽

10.18632/oncotarget.7633 ◽

2016 ◽

Vol 7 (14) ◽

pp. 18050-18064 ◽

Cited By ~ 29

Author(s):

Peng Zou ◽

Yiqun Xia ◽

Weiqian Chen ◽

Xi Chen ◽

Shilong Ying ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Thioredoxin Reductase ◽

Gastric Cancer Cells ◽

Thioredoxin Reductase 1

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A thioredoxin reductase inhibitor ethaselen induces growth inhibition and apoptosis in gastric cancer

Journal of Cancer ◽

10.7150/jca.40744 ◽

2020 ◽

Vol 11 (10) ◽

pp. 3013-3019

Author(s):

Wang Wu ◽

Zhiying Yang ◽

Xing Xiao ◽

Tailai An ◽

Bo Li ◽

...

Keyword(s):

Gastric Cancer ◽

Growth Inhibition ◽

Reductase Inhibitor ◽

Thioredoxin Reductase

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Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02052-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Haiyong Zhang ◽

Jing Wu ◽

Jinqiu Yuan ◽

Huafu Li ◽

Yawei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Growth ◽

Growth Inhibition ◽

Cancer Cells ◽

Nude Mice ◽

Combined Treatment ◽

Thioredoxin Reductase ◽

Tumor Growth Inhibition ◽

Gastric Cancer Cells

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

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Ultrastructural Cytochemical Study of Human Gastric Cancer: Observation of AKP ase,ACP ase,G6P ase,TPP ase and CO ase

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158819 ◽

1990 ◽

Vol 48 (3) ◽

pp. 254-255

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Du Wei Dong ◽

Xu Ai Liam

Keyword(s):

Gastric Cancer ◽

Gastric Epithelium ◽

Human Gastric Cancer ◽

Electron Microscopic ◽

Cytochemical Study ◽

Electron Microscopic Cytochemistry ◽

Cytochemical Reaction ◽

Set Up ◽

Cancer Tissues ◽

Cytochemical Technique

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.

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Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158807 ◽

1990 ◽

Vol 48 (3) ◽

pp. 252-253

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Wu Jifeng ◽

Chen Xiaolin

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Cancer Cells ◽

Microscopic Observation ◽

Biological Significance ◽

Ultrastructural Localization ◽

Mucinous Carcinoma ◽

Surface Glycoprotein ◽

Tubular Adenocarcinoma ◽

Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

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