Tumor heterogeneity is a major challenge for breast cancer researchers who have struggled to find effective treatments despite recent advances in oncology. Although the use of 2D cell culture methods ...in breast cancer research has been effective, it cannot model the heterogeneity of breast cancer as found within the body. The development of 3D culture of tumor cells and breast cancer organoids has provided a new approach in breast cancer research, allowing the identification of biomarkers, study of the interaction of tumor cells with the microenvironment, and for drug screening and discovery. In addition, the possibility of gene editing in organoids, especially using the CRISPR/Cas9 system, is convenient, and has allowed a more detailed study of tumor behavior in models closer to the physiological condition. The present review covers the application of organoids in breast cancer research. The recent use of gene-editing systems to provide insights into therapeutic approaches for breast cancer, is highlighted. The study of organoids and the possibility of gene manipulation may be a step towards the personalized treatment of breast cancer, which has so far remained unattainable due to the high heterogeneity of breast cancer.
Matrix metalloproteinases (MMPs) play key roles in epithelial-mesenchymal transition (EMT) for the development of cancer cell invasion and metastasis. MMP-13 is an extracellular matrix ...(ECM)-degrading enzyme that plays crucial roles in angiogenesis, cell cycle regulation, niche maintenance, and transforming squamous epithelial cells in various tissues. CD44, a transmembrane glycoprotein expressed on esophageal tumor cells, is required for EMT induction and invasion in esophageal squamous cell carcinoma (ESCC). The transcription factor TWIST1, as EMT and stemness marker, regulates MMPs expression and is identified as the downstream target of CD44. In this study, we aimed to investigate the probable interplay between the expression of key genes contributing to ESCC development, including MMP-13, TWIST1, and CD44 with clinical features for introducing novel diagnostic and therapeutic targets in the disease. The gene expression profiling of
MMP-13
,
TWIST1,
and
CD44
was performed using quantitative real-time PCR in tumor tissues from 50 ESCC patients compared to corresponding margin non-tumoral tissues. Significant overexpression of
MMP-13, CD44S, CD44V3, CD44V6,
and
TWIST1
were observed in 74%, 36%, 44%, 44%, and 52% of ESCC tumor samples, respectively. Overexpression of
MMP-13
was associated with stage of tumor progression, metastasis, and tumor location (
P
< 0.05). There was a significant correlation between
TWIST1
overexpression and grade (
P
< 0.05). Furthermore, overexpression of
CD44
variants was associated with stage of tumor progression, grade, tumor invasion, and location (
P
< 0.05). The results indicated the significant correlation between concomitant expression of
MMP-13/TWIST1
,
TWIST1/CD44
, and
CD44/MMP-13
with each other in a variety of clinicopathological traits, including depth of tumor invasion, tumor location, stage of tumor, and lymph node involvement in ESCC tissue samples (
P
< 0.05). Collectively, our results indicate that the TWIST1-CD44-MMP-13 axis is involved in tumor aggressiveness, proposing these genes as regulators of EMT, diagnostic markers, and therapeutic targets in ESCC.
Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. ...Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source ...of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH.
This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay.
The levels of MDA (
< 0.001), MPO activity (
< 0.001), thiol (
< 0.001), NO (
< 0.01), and PAB (
< 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (
< 0.001) and PAB (
< 0.001) when compared to healthy subjects. Elevated levels of MDA (
< 0.001) and PAB (
< 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979;
= 0.033), and MDA (OR: 0.996;
= 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished.
Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.
Background: Breast cancer represents the most prevalent cancer among women and ranks as the third leading cause of cancer-related mortality in females. Given the critical role of early cancer ...detection, identifying biomarkers related to breast cancer is essential for prognosis and early identification. This study aims to explore the differential expression of the estrogen receptor-β (ESRβ) gene in cancerous tissue samples compared to standard tissue samples, aiming to identify a biomarker for predicting cancer prognosis.Method: This study collected 60 fresh tissue samples from breast cancer patients post-surgery, comprising 30 tumor samples and 30 standard samples adjacent to the tumor, which were immediately stored at -70 °C. Following RNA extraction and cDNA synthesis, the expression levels of the ESRβ gene and the Gapdh gene (as an internal control) were analyzed using the real-time polymerase chain reaction method.Results: The study examined the variation in ESRβ gene expression between tumor tissues and adjacent healthy tissues in breast cancer patients. An increase in gene expression was observed in tumor samples compared with the adjacent healthy tissue. Furthermore, statistical analysis using SPSS software revealed a significant correlation between the gene expression level and tumor grade across all examined groups. Additionally, the findings indicate a significant difference in gene expression between patients with and without tumor metastasis.Conclusion: The ESRβ gene holds potential as a biomarker for breast cancer prognosis.
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•The most typical malignancy among women worldwide is breast cancer.•Estrogen receptor play an vital role in breast cancer.•Phosphorylation is affect the activity of Estrogen ...receptor.•Hesperidin is a glycosylated flavanone found in citrus fruits with anticancer effects.
The most common malignancy among women worldwide is breast cancer. The estrogen receptor plays a vital role in this cancer. One of the most well-known mechanisms that affects the activity of this receptor is its phosphorylation by protein kinase pathways. Hesperetin, a flavonoid abundant in citrus species such as lemons, grapefruits, and oranges, is the aglycone form of hesperidin. It has undergone thorough evaluation for its potential anti-cancer properties, particularly in the context of breast cancer. Studies have shown that hesperetin has an effect on intracellular kinase pathways. The aim of this study was to investigate the effect of hesperetin on the expression, phosphorylation and activity of estrogen receptor alpha (ERα) in MCF-7 breast cancer cell line.
MCF-7 cells were cultured in RPMI-1640 phenol red-free medium supplemented with charcoal-stripped FBS and treated with hesperetin. The MTT method was used to evaluate cell survival. The levels of the ERα protein and its phosphorylated form (Ser118) were determined via western blotting. A luciferase reporter vector was used to evaluate ERE activity.
The results of this study indicated that hesperetin reduced the survival of MCF-7 cells in a dose-dependent manner. The expression and phosphorylation (at Ser118) of the ERα significantly increased and decreased, respectively, in the groups treated with hesperetin. Hesperetin increased the activity of the ERα in the absence of E2, although these differences were not statistically significant. Conversely, in the presence of E2, hesperetin caused a significant decrease in receptor activity.
Based on the results of this study, it can be concluded that hesperetin has a significant effect on ERα expression, phosphorylation and activity.
Background: The development of allergic rhinitis (AR) is caused by the interaction between genetic predisposition and environmental factors. In this study, the association between GATA3 single ...nucleotide polymorphisms and AR in an Iranian population was identified. Methods: This case-control study was performed on 86 patients with AR and 86 healthy subjects. This study aimed to evaluate a potential association between two GATA3 SNPs, rs1269486 and rs2229360, and AR. Blood samples were collected and DNA was extracted for the evaluation of these SNPs by RFLP-PCR. Results: A statistically-significant association was found between rs1269486 and AR (P<0.001). The frequencies of the A and GA genotypes were less in patients than in controls. The frequencies of the G allele and the GG genotype were greater in patients than in controls (P < 0.001). Conclusions: SNP rs1269486 of GATA3 was associated with AR and sensitivity to aeroallergens in our population. Because of the significance of this gene in AR, studying the association between GATA3 polymorphisms and AR is recommended for other populations.
CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along with CD44V3 influence the cell motility, migration, and adhesion, while in tumor cells they lead to tumor invasion, ...progression, and metastasis. The purpose of this research is to evaluate the CD44S and CD44V3 expression in Esophageal Squamous Cell Carcinoma (ESCC) and to reveal their correlations with clinicopathological features of patients.
Fresh tumoral and distant tumor-free esophageal tissues were obtained from 50 patients with ESCC. Using quantitative real-time PCR, the expression levels of CD44S and CD44V3 were quantified and compared in both groups of cells. The patients had not received any therapeutic interference, such as chemotherapy or radiation, prior to sampling.
Significant overexpression of CD44S and CD44V3 mRNA was observed in 13 (26.0%, P=0.03) and 11 (22.0%, P=0.007) tumor specimens, respectively. The expression of the genes were significantly correlated not only with each other (P=0.0001), but also with differentiation grade of tumor (P=0.033), stage of tumor progression (P=0.003), and depth of tumor invasion (P=0.00). In addition, low level of CD44V3 mRNA expression was attended to be associated with tumor invasion.
There is no correlation between CD44S expression with clinicopathological features of patients; however, simultaneous expression of these genes has an important effect on tumorigenesis.
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