Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma

Montalvo-Javé, Eduardo E.; Olguín-Martínez, Marisela; Hernández-Espinosa, Diego Rolando; Sánchez-Sevilla, Lourdes; Mendieta-Condado, Edgar; Contreras-Zentella, Martha Lucinda; Oñate‐Ocaña, Luis F.; Escalante-Tatersfield, Tomás; Echegaray-Donde, Agustín; Ruiz-Molina, Juan Manuel; Herrera, Miguel F.; Morán, Julio; Hernández‐Muñoz, Rolando

doi:10.1016/j.ejca.2015.11.027

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…33 This phenomenon may be the common mechanism by which GPx2 promotes malignancy in these gland cell-derived carcinomas susceptible to oxidative stress. [34][35][36] However, the specific underlying mechanisms remain to be determined. In summary, our findings indicate that GPx2 expression levels are increased in both primary tumor foci and lymphatic metastases in GC and are strongly correlated with various clinicopathological characteristic associated with tumorigenesis and aggressiveness, including the Ki-67 labeling index, tumor differentiation, tumor histological patterns, Lauren classifications, LN metastasis, vascular invasion, TNM stages, and H. pylori infection.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of glutathione peroxidase 2 in gastric carcinoma

et al. 2017

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Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values < 0.05). Furthermore, Pearson's chi-square tests, as well as Spearman's correlation analysis, revealed that glutathione peroxidase 2 expression levels were strongly correlated with the Ki-67 labeling index, differentiation, histological patterns, Lauren classifications, lymph node metastasis, vascular invasion, tumor-node-metastasis stages, Helicobacter pylori infection, and overall survival (all p values < 0.05). Kaplan-Meier analysis, as well as the log-rank test and multivariate Cox regression analysis, showed that multiple clinicopathological risk factors and glutathione peroxidase 2 expression were novel independent prognostic factors for gastric carcinoma (all p values < 0.05). Glutathione peroxidase 2 expression is a novel independent prognostic biomarker for gastric carcinoma that may be used to devise personalized therapeutic regimens and precision treatments for this disease.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of glutathione peroxidase 2 in gastric carcinoma

et al. 2017

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“…Investigators have also reported pathological roles of NOX2 in malignancies. For example, NOX2-derived ROS facilitate the metastasis of melanoma cells, by downmodulation of NK-cell function [ 53 ], immunosuppression by chronic myelomonocytic leukemia (which depends on NOX2 [ 54 ]), and cell proliferation—which is associated with NOX2 in gastric cancer [ 55 ].…”

Section: Nox and Urological Cancermentioning

confidence: 99%

A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis

Miyata

Matsuo

Sagara

et al. 2017

IJMS

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Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and NADPH oxidases (NOXs), which are one of the most important sources of ROS. Oxidative stress plays important roles in the etiologies, pathological mechanisms, and treatment strategies of vascular diseases. Additionally, oxidative stress affects mechanisms of carcinogenesis, tumor growth, and prognosis in malignancies. Nearly all solid tumors show stimulation of neo-vascularity, termed angiogenesis, which is closely associated with malignant aggressiveness. Thus, cancers can be seen as a type of vascular disease. Oxidative stress-induced functions are regulated by complex endogenous mechanisms and exogenous factors, such as medication and diet. Although understanding these regulatory mechanisms is important for improving the prognosis of urothelial cancer, it is not sufficient, because there are controversial and conflicting opinions. Therefore, we believe that this knowledge is essential to discuss observations and treatment strategies in urothelial cancer. In this review, we describe the relationships between members of the NOX family and tumorigenesis, tumor growth, and pathological mechanisms in urological cancers including prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, we introduce natural compounds and chemical agents that are associated with ROS-induced angiogenesis or apoptosis.

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“…Relationship between the expression of NOX1 in the stroma of GBC and clinicopathological parameters in patients with GBCs. development through the generation of ROS and important intracellular signaling molecules (27,28), has been reported to be highly expressed in a variety of tumor types such as gastric (29)(30)(31) and liver cancers (32), and is associated with the poor prognosis of these patients. However, these studies mainly focused on the expression of NOX1 in the tumor cells themselves.…”

Section: Discussionmentioning

confidence: 99%

“…NOX-dependent ROS regulation abnormalities are thought to be closely associated with tumor development (27,28). NOX1 has been reported to be highly expressed in a variety of tumor types including gastric (29)(30)(31) and liver cancer (32), and is associated with poor prognosis. However, tumor stromal NOX1 expression and its relationship with the prognosis of tumor patients have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis

et al. 2019

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Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer-associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) expression has been reported to be involved in tumorigenesis and useful for tumor prognosis. However, NOX1 expression in the stroma of GBCs, particularly gallbladder cancer-associated fibroblasts (GCAFs), and its prognostic significance in GBC patients remains unclear. In the present study, NOX1 expression in the stroma of human gallbladder lesions in vivo was investigated, as well as in GCAFs and co-cultures of GBC-SD+GCAFs in vitro, and their correlation with clinicopathological parameters and the prognosis of GBC patients were evaluated. The results revealed that NOX1 expression was significantly upregulated in the stroma of GBCs compared with precancerous and benign lesions of the gallbladder; NOX1 expression was localized to gallbladder stromal fibroblasts expressing α-smooth muscle actin and fibroblast secreted protein-1. Furthermore, these observations were confirmed by the fact that NOX1 expression was upregulated in GCAFs as determined by Affymetrix gene profile chip analysis and reverse transcription-quantitative PCR. In addition, overexpression was observed in formed spheroids of GBC-SD+GCAF co-cultures by immunohistochemistry and western blotting in vitro. Thus, it was verified that NOX1 expression was upregulated in GCAFs. Furthermore, upregulated stromal NOX1 expression was correlated with aggressive characteristics such as differentiation degree (P=0.042), venous invasion (P=0.041), resection methods (P=0.002), and a lower survival rate (P=0.025, log-rank test) of patients with GBC. Stromal NOX1 expression (P=0.047) was an independent prognostic factor for the overall survival rate of patients with GBC. GBC patients with upregulated NOX1 expression in GCAFs had a poorer prognosis. These results revealed that stromal NOX1 may be a novel biomarker and/or target, and may contribute to the discovery of new tumor markers and potential targeted therapeutics for human GBCs.

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Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma

Cited by 12 publications

References 38 publications

Prognostic significance of glutathione peroxidase 2 in gastric carcinoma

Prognostic significance of glutathione peroxidase 2 in gastric carcinoma

A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis

Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis

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