Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

Hwang, Na Rae; Chung, Sung Min

doi:10.5483/bmbrep.2020.53.5.041

Cited by 12 publications

(12 citation statements)

References 13 publications

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“…TLR4 was directly related with NLRP3 and PYCARD demonstrated a positive synergistic correlation supporting malignant phenotypes, although the correlation factor was not strong. Reciprocal crosstalk between the NLRP3 inflammasome and TLR4 is not a surprise in other malignancies ( 40 , 41 ) but for the first time, we found a direct indication of their interaction in our BC patients.…”

Section: Discussionsupporting

confidence: 67%

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

et al. 2021

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Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p<0.0001). All the proteins were associated to more aggressive clinicopathological characteristics (tumor size, grade, tumor proliferative activity etc.). Univariate analyses were carried out and related Kaplan-Meier curves plotted for NLRP3, PYCARD and TLR4 expression. Patients with higher NLRP3 and TLR4 expression had worse 5-year disease-free survival (DFS) compared to patients with lower NLRP3 and TLR4 expression (p =0.021 and p = 0.009, respectively). In multivariate analysis, TLR4 was confirmed as independent prognostic factors for DFS (HR = 2.03, 95% CI 1.16–3.57, p = 0.014), and high NLRP3 expression showed a slight association with DFS (HR = 1.75, 95% CI 0.98–3.15, p = 0.06). In conclusion, we showed TLR4 expression as independent prognostic factors and we highlighted for the first time that high expression of NLRP3 is linked to a poor prognosis in BC patients. These results suggest that NLRP3 and TLR4 could be two new good prognostic factor for BC patients.

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Section: Discussionsupporting

confidence: 67%

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

et al. 2021

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“…In the development of cancer, the expression level of GSDMs in cancer cells is usually lower than that in normal tissues due to the high methylation of the promoters of pyroptosis-related genes, resulting in the growth and metastasis of tumors ( Kim et al, 2008 ; Croes et al, 2017 ). Chemotherapy drugs and tamoxifen can inhibit the progression of tumors by inducing pyroptosis of tumor cells ( Hu et al, 2020 ; Hwang and Chung, 2020 ). It has been proven that the expression level of GSDMs was closely related to the prognosis of BC ( de Beeck et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer

Ping

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Background: Pyroptosis, a kind of programmed cell death characterized by the rupture of cell membranes and the release of inflammatory substances, plays an important role in the occurrence and development of cancer. However, few studies focus on the pyroptosis-associated long non-coding RNAs (lncRNAs) in breast cancer (BC). The prognostic value of pyroptosis-associated lncRNAs and their relationship with tumor microenvironment (TME) in BC remain unclear. The purpose of this study was to explore the prognostic role of pyroptosis-associated lncRNAs and their relationship with TME in BC.Methods: The transcriptome data and clinical data of female BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 937 patients were randomly assigned to either training set or validation set. A pyroptosis-associated lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis and immune microenvironment analysis related to pyroptosis-associated lncRNAs were performed. A nomogram based on the risk score and clinical characteristics was established.Results: A 9-pyroptosis-associated lncRNA signature was constructed to separate BC patients into two risk groups. High-risk patients had poorer prognosis than low-risk patients. The risk score was proven to be an independent prognostic factor by multivariate Cox regression analysis. Function analysis and immune microenvironment analysis showed that low-risk BC tended to be an immunologically “hot” tumor. A nomogram was constructed with risk score and clinical characteristics. Receiver operating characteristic curve (ROC) analysis demonstrated credible predictive power of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.880 at 1 year, 0.804 at 3 years, and 0.769 at 5 years in the training set, and 0.799 at 1 year, 0.794 at 3 years, and 0.728 at 5 years in the validation set.Conclusion: We identified a novel pyroptosis-associated lncRNA signature that was an independent prognostic indicator for BC patients. Pyroptosis-associated lncRNAs had potential relationship with the immune microenvironment and might be therapeutic targets for BC patients.

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“…It locally secretes complement components as C1q, complement factor B (CFB), complement component 4 (C4), CFI, and CFH [ 20 , 21 , 22 , 23 ]. We and others showed that complement secretion is modified by external stress [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Additionally, generation of complement activation products, such as anaphylatoxins and opsonins, by healthy and stressed RPE cells independent of any external complement source is described [ 21 , 24 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells

et al. 2020

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The retinal pigment epithelium (RPE) maintains visual function and preserves structural integrity of the retina. Chronic dysfunction of the RPE is associated with retinal degeneration, including age-related macular degeneration (AMD). The AMD pathogenesis includes both increased oxidative stress and complement dysregulation. Physiological sources of oxidative stress in the retina are well known, while complement sources and regulation are still under debate. Using human primary RPE (hpRPE) cells, we have established a model to investigate complement component expression on transcript and protein level in AMD-risk and non-risk hpRPE cells. We evaluated the effect of properdin, a complement stabilizer, on the hpRPE cell-dependent complement profile exposed to oxidative stress. hpRPE cells expressed complement components, receptors and regulators. Complement proteins were also stored and secreted by hpRPE cells. We associated AMD-risk single nucleotide polymorphisms with an increased secretion of complement factors D (CFD) and I (CFI). Furthermore, we detected hpRPE cell-associated complement activation products (C3a, C5a) independent of any extracellularly added complement system. Exogenous properdin increased the mRNA expression of CFI and CFD, but decreased levels of complement components (C1Q, C3), receptors (C3AR, C5AR1, CD11B) and inflammation-associated transcripts (NLRP3, IL1B) in hpRPE cells exposed to oxidative stress. This properdin effect was time-dependently counter regulated. In conclusion, our data unveiled a local, genotype-associated complement component production in hpRPE cells, regulated by exogenous properdin. The local complement production and activation via blood-independent mechanisms can be a new therapeutic target for AMD.

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Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

Cited by 12 publications

References 13 publications

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer

Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells

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