scholarly journals Associations between the Levels of Estradiol-, Progesterone-, and Testosterone-Sensitive MiRNAs and Main Clinicopathologic Features of Breast Cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 4
Author(s):  
Tatiana Kalinina ◽  
Vladislav Kononchuk ◽  
Efim Alekseenok ◽  
Grigory Abdullin ◽  
Sergey Sidorov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Sites ◽  
Bioinformatic Analysis ◽  
Mirna Expression Profile ◽  
Lymph Node Status ◽  
Promoter Regions ◽  
Ki 67 ◽  
Breast Tumor Tissue ◽  
The Status ◽  
Mcf 7

Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis. Therefore, to search for miRNAs that may function as markers in BC, using bioinformatic analysis and the literature data, we selected 13 miRNAs whose promoter regions contain binding sites for ER or AR, or putative binding sites for ER, AR, and PR. We quantified their expression in MCF-7 cells treated with estradiol, progesterone, or testosterone. The levels of miRNAs sensitive to one or more of these hormones were quantified in BC samples (n = 196). We discovered that high expression levels of miR-190b in breast tumor tissue indicate a positive ER status, and miR-423 and miR-200b levels differ between patients with and without HER2 amplification. The miR-193b, -423, -190a, -324, and -200b levels were associated with tumor size or lymph node status in BC patients, but the presence of these associations depended on the status and expression level of ER, PR, HER2, and Ki-67. We also found that miR-21 expression depends on HER2 expression in ER- and/or PR-positive BC. The levels of miRNA were significantly different between HER2 0 and HER2 1+ tumors (p = 0.027), and between HER2 0 and HER2 2+, 3+ tumors (p = 0.005).

scholarly journals Ki-67 status in patients with primary breast cancer and its relationship with other prognostic factors

2019 ◽  
Vol 6 (2) ◽  
pp. 2986-2991 ◽  
Author(s):  
Touraj Asvadi Kermani ◽  
Iraj Asvadi Kermani ◽  
Zhaleh Faham ◽  
Roya Dolatkhah
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Primary Breast Cancer ◽  
Tumor Biology ◽  
Lymph Node Status ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Patients With Cancer ◽  
The Status ◽  
Optimal Therapeutic Strategy

Introduction: Breast cancer (BC) is the most common cancer in women and is the second most common cause of fatality in patients with cancer in the world. Cell proliferation plays an important role in the clinical behavior of invasive BC. We aimed to assess the status of Ki-67 in patients with primary breast cancer and evaluate the association of this tumor marker with other clinico-pathologic and prognostic factors. Methods: The current study recruited 220 patients with primary BC admitted to the oncology clinic of the Tabriz University of Medical Sciences. We evaluated Ki-67 IHC slides and reported the Ki-67 status and its relationship with other prognostic factors in breast cancer patients. Among 220 patients, 63.3% developed grade 2 tumors, and 63.8% were younger than 50-year-olds. 117 cases (53%) were Ki-67 positive with more than 1% tumor nuclei stained, and 53 cases (24%) had tumors with more than 15% of Ki-67 expression. Results: There was no correlation between Ki-67 and patient's age (Spearman rho = 0.375, tau Kendall = 0.374), tumor size (Spearman rho = 0.558, tau Kendall = 0.548) and grade (Spearman rho = 0.570, tau Kendall = 0.568), however, there was a marginally significant relationship between lymph node status and Ki-67 expression (Spearman rho = 0.077, tau Kendall = 0.079). Based on the Mann -Whitney test, there was a significant correlation between the expression of estrogen receptor (ER) and progesterone receptor (PR) with Ki-67. Conclusion: A reliable estimation of different prognostic factors in BC patients is required for the selection of an optimal therapeutic strategy. The attention has been focused on the markers of tumor biology.  

scholarly journals Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
Tumor Growth Inhibition ◽  
Autophagic Flux ◽  
Ki 67 ◽  
Mcf 7

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

scholarly journals Prominent Prognostic Factors in Aggressive Breast Cancer: A Review

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Kazem Nejati ◽  
Sedigheh Fekri Aval ◽  
Mohammadreza Alivand ◽  
Abolfazl Akbarzadeh ◽  
AmirAhmad Arabzadeh
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Lymph Node Status ◽  
Cancer Type ◽  
Ki 67 ◽  
Increased Risk ◽  
Aggressive Breast Cancer ◽  
Breast Cancer Type

Context: Breast cancer (BC) is the most common cancer in women worldwide. Hereditary susceptibility created by mutations in autosomal dominant genes is responsible for 5 to 10% of all BC cases in women. Recent studies have identified genes associated with increased risk for aggressive BC, providing the basis for better risk management. Evidence Acquisition: The latest information in National Center for Biotechnology Information (NCBI), Google Scholar, ScienceDirect, and Scopus were the main databases for finding articles. A combination of keywords of ‘metastasis’, ‘invasion’, ‘aggressive breast cancer’, ‘prognostic factor’, ‘mutation’, and ‘cancer treatment’ was searched in the databases to identify related articles. Titles and abstracts of the articles were studied to choose the right articles. Results: Mutations in breast cancer type 1 susceptibility protein (BRCA1) and breast cancer type 2 susceptibility protein (BRCA2) genes are two central players related to the high risk of BC. Mutation in tumor protein p53 (TP53) is another important mutation that leads to triple-negative BC. Although the majority of BC types are not associated with high-throughput mutant genes such as BRCA1, BRCA2, and TP53, they are associated with low-throughput genes, including DNA repair protein Rad50 (RAD50), Nijmegen breakage syndrome gene (NBS1), checkpoint kinase 2 (CHEK2), BRCA1-interacting protein 1 (BRIP1), E-cadherin gene (CDH1) and PALB2, UCHL1, aldehydedehydrogenase1A3 (ALDH1A3), androgen receptor (AR), 5-bisphosphate 3-kinase (PIK3CA), phosphatidylinositol-4, and luminal gene expression that are generally mutated in the global population. High tumor mutational burden (TMB) was associated with improved progression-free survival. Conclusions: The lymph node status, early tumor size, ER, PR, human epidermal growth factor receptor-2 (HER2), and Ki-67 are conventional prognostic factors for BC. However, these factors cannot exactly predict the aggressive behavior of BC. Hence, in this review, we discussed new prognostic factors of aggressive BCs that are useful for the treatment of patients with BC.

scholarly journals LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yufei Lv ◽  
Xiaohong Lv ◽  
Huike Yang ◽  
Xiuying Qi ◽  
Xiangchen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Binding Sites ◽  
Luciferase Reporter ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cell ◽  
Ki 67 ◽  
Cancer Data ◽  
Tnbc Cell ◽  
Direct Binding

BackgroundTriple-negative breast cancer (TNBC) is a significant cause of patient morbidity. The exactly pathobiological features of this condition has yet to be completely elucidated.MethodsBreast cancer data obtained from The Cancer Genome Atlas (TCGA) database were evaluated for lncRNA SNHG6 expression. Normal human breast epithelial cell line (MCF-10A) and other breast cancer cell lines (BT-549, MDA-MB-231, Hs 578t, ZR-75-30, SK-BR-3, MCF-7) were also assessed for lncRNA SNHG6 expressions. Cellular proliferative ability was evaluated with colony formation and CCK-8 assays. The ability of cells to migrate was scrutinized with the wound healing and Boyden chamber cell migration assays. qRT-PCR enabled for detection of lncRNA SNHG6, miR-125b-5p and BMPR1B mRNA expressions. Protein BMPR1B expressions were further assessed using Western Blotting. Direct binding sites between transcripts were determined using dual-luciferase reporter assays. We also constructed a xenograft mouse model to further dissect the vivo implications of lncRNA SNHG6. Ki-67 and c-Caspase-3 expressions were detected using immunohistochemistry staining.ResultsBreast cancer cell lines demonstrated higher lncRNA SNHG6 expressions, particularly TNBC cell lines, in contrast to normal breast epithelial cell lines. This finding coincided with those noted on analysis of TCGA breast cancer data. lncRNA SNHG6 knockdown inhibited TNBC cell proliferation, migration, while promoted cell apoptosis. Furthermore, suppressed lncRNA SNHG6 expressions resulted in lower tumor weights and volumes in a xenograft mouse model, as evidenced by Ki-67 and c-Caspase-3 expression profiles in tumor tissues. miR-125b-5p and lncRNA SNHG6/BMPR1B both possessed direct binding sites for each other which was validated utilizing a dual-luciferase reporter assay. Decreasing lncRNA SNHG6 expression in TNBC cells upregulated miR-125b-5p expression. Another side, inhibiting miR-125b-5p upregulated BMPR1B expression in these cells. Moreover, knocking down lncRNA SNHG6 downregulated BMPR1B expression in TNBC cells, and the finding was rescued in cells which were exposed to miR-125b-5p inhibitor. Downregulating miR-125b-5p mitigated the effect of suppressing lncRNA SNHG6 on TNBC cell proliferation, migration, and apoptosis.ConclusionDownregulation of lncRNA SNHG6 could inhibit TNBC cell proliferative, migratory capabilities and promote apoptosis capability, likely through modulation of the miR-125b-5p/BMPR1B axis. This axis may be targeted in formulating new therapies for TNBC.

scholarly journals An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERα action and associates with the sensitivity of antiestrogen in breast cancer

2020 ◽  
Vol 48 (19) ◽  
pp. 10768-10784
Author(s):  
Ge Sun ◽  
Chunyu Wang ◽  
Shengli Wang ◽  
Hongmiao Sun ◽  
Kai Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Binding Sites ◽  
Estrogen Receptor Alpha ◽  
Target Genes ◽  
Regulatory Element ◽  
Therapy Resistance ◽  
Ctcf Binding ◽  
Promoter Regions ◽  
Positive Breast Cancer

Abstract Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.

Luminal A and Luminal B subtypes in patients with breast cancer 65 years of age and older.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 549-549
Author(s):  
Robert Konigsberg ◽  
Georg Pfeiler ◽  
Nicole Hammerschmid ◽  
Tatjana Klement ◽  
Christian Dittrich
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Endocrine Therapy ◽  
Tumor Size ◽  
Lymph Node Status ◽  
Primary Therapy ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Significant Difference

549 Background: In 2011, the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer (bc) suggested the distinction between Luminal A and Luminal B subtypes. In Luminal A patients (pts) endocrine therapy seems to be sufficiently effective, whereas in Luminal B pts the additional application of chemotherapy should be considered. It is currently unknown, whether the risk stratification into Luminal A and B is comparably or more discriminatory than the established pathologic tumor size (pT) and lymph node (pN) status in pts ≥ 65 years. This analysis evaluates the discriminatory capacity of the new distinction between Luminal A and B and the established prognostic factors in bc pts ≥ 65 years treated with endocrine therapy only. Methods: Clinico-pathological data of 190 bc pts ≥ 65 years diagnosed between 1998 and 2004 were retrospectively analyzed. Pts were classified as Luminal A [ER (+) and/ or PR (+) and Her/2neu (-) and Ki-67 < 14%] or Luminal B [ER (+) and/ or PR (+) and Her2 (-) and Ki-67 ≥ 14%]. The Kaplan-Meier method was used to assess the progression-free survival (PFS) and overall survival (OS) estimates. Differences in survival between groups were tested for significance by the log-rank test. Results: Median age was 74 years (65–92 years) and median time of follow-up was 69 months (0–134 months). 68.9% and 31.1% pts had Luminal A and B subtypes, respectively. 73.3% and 26.7% of pts had pT1 and pT2 tumors, respectively. 79.7% and 20.3% of pts had pN0 and pN1 status, respectively. Overall, median PFS was 33 months. No significant difference regarding PFS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.458; 0.172; 0.156), respectively. Overall, median OS was not reached. No significant difference regarding OS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.328; 0.951; 0.976), respectively. Conclusions: In bc pts ≥ 65 years treated with endocrine therapy only, neither the recently consented dichotomization into Luminal A and B subtypes nor pathologic tumor size and lymph node status could be confirmed to be discriminative as propagated in the 2011 St. Gallen Consensus for the overall bc population.

Breast cancer in "young" women: Age cutoff and clinicopathologic features.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12019-e12019
Author(s):  
Gang Nie ◽  
Haibo Wang ◽  
Yuhua Song ◽  
Yan Mao ◽  
Weihong Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Family History ◽  
Cancer Patients ◽  
Older Patients ◽  
Age Groups ◽  
Her2 Status ◽  
Lymph Node Status ◽  
Breast Cancer Patients ◽  
Ki 67

e12019 Background: Age of patients play a key role in outcome of breast cancer, and therefore influences choice of treatment. In most studies, "young" is defined as being below 40 or 35 years. However, there are conflicts concerning definition of younger and older patients. In this study, we aim to establish a more appropriate age cut-off between “younger” and “older” breast cancer patients. Methods: A total of 5984 female breast cancer patients recruited in the Breast Cancer Registry of the Affiliated Hospital of Qingdao University during 2008 to 2014 were enrolled. Patients were divided into 11 groups by every 5 years’ age difference. The clinical characteristics and overall survival (OS) were compared among these age groups. Results: Among the five groups under age 45 (n = 1771, 30.0%), larger proportion of patients underwent breast conservation surgery in the “30-34” group (p = .027), and more patients were found with family history in the “25-29” group than in other groups (p = .029). No significant difference was found in OS (p = .059), clinicopathological stage, lymph node status, ER/PR status, HER2 status, or Ki-67 status among those five groups. For patients above 45 (n = 4813, 70.0%), differences were found in OS (p = .001) and significant differences with clinicopathological features (lymph node status, ER/PR status, HER2 status and Ki-67 status) were shown between younger and the older age groups (p = .001) among the six groups, except for family history (p = .066). Conclusions: Clinicopathological characteristics and survival status are similar among breast cancer patients under 45 years and vitiate among older patients. Age 45 is an appropriate cut-off for clinical grouping of breast cancer patients by age .

Expression of Phosphatase and Tensin Homolog Deleted on Chromosome Ten on the Development of Cisplatin Resistance in Breast Cancer by TGF-β1 Signal Pathway

2021 ◽  
Vol 11 (10) ◽  
pp. 1900-1907
Author(s):  
Yuan-Ding Zhang ◽  
Zhen-Xia Wang ◽  
Yan Zhang ◽  
Jin Pei
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cisplatin Resistance ◽  
Signal Pathway ◽  
Lymph Node Status ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Introduction: This study aims to evaluate the expression of PTEN on the development of cisplatin resistance in breast cancer by TGF-β1 signal pathway in order to investigate the prognostic value of PTEN and TGF-β1 for breast cancer. Material and Methods: In this study, HE staining, Immunohistochemical staining, Immunofluorescence and Western blotting were used to detect the expression of PTEN and TGF-β1 in breast cancer MCF-7 cells to explain clearly the relationship between PTEN and TGF-β1 on TGF-β1 treated MCF-7 Cells. Results: The experiment results showed the expression of PTEN and TGF-β1 in Human breast cancer increased obviously compared with paracancerous tissues (P < 0.05). The expression of PTEN and TGF-β1 was closely correlated with tumor size, distant metastasis, pathological stage and progesterone receptor status, but not with age and lymph node status. At the same time, the expression of PTEN and TGF-β1 in cisplatin-treated MCF-7 Cells reduced as compared with untreated breast cancer cells (P < 0.05). In addition, the expression of PTEN increased by TGF-β1 inducer treated Human Breast Cancer Cells. However, the expression of PTEN in TGF-β1 inhibitor treated Human Breast Cancer Cells was lower than in untreated breast cancer cells (P < 0.05). Conclusions: PTEN and TGF-β1 played an important role in Human Breast cancer. In addition, the expression of PTEN could be regulated by TGF-β1 in Cisplatin and TGF-β1 treated Human Breast Cancer Cells.

Quantitative analysis of shear wave elastic heterogeneity for prediction of lymphovascular invasion in breast cancer

2021 ◽  
pp. 20210682
Author(s):  
Yini Huang ◽  
Yubo Liu ◽  
Yun Wang ◽  
Xueyi Zheng ◽  
Jing Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Predictive Value ◽  
Shear Wave ◽  
Predictive Value ◽  
Lymphovascular Invasion ◽  
Imaging Biomarker ◽  
Lymph Node Status ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Ki 67

Objective: To evaluate the correlation between elastic heterogeneity (EH) and lymphovascular invasion (LVI) in breast cancers and assess the clinical value of using EH to predict LVI pre-operatively. Methods: This retrospective study consisted of 376 patients with breast cancers that had undergone shear wave elastography (SWE) with virtual touch tissue imaging quantification between June 2017 and June 2018. The EH was determined as the difference between the averaged three highest and three lowest shear wave value. Clinicalpathological parameters including histological type and grades, LVI, axillary lymph node status and molecular markers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67) were reviewed and recorded. Relationship EH and clinicalpathological parameters was investigated respectively. The diagnostic performance of EH in distinguishing LVI or not was analyzed. Results: At multivariate regression analysis, only EH (p = 0.017) was positively correlated with LVI in all tumors. EH (p = 0.003) and Ki-67 (p = 0.025) were positively correlated with LVI in tumors ≤ 2 cm. None of clinicalpathological parameters were correlated with LVI in tumors > 2 cm (p > 0.05 for all). Using EH to predict LVI in tumors ≤ 2 cm, the sensitivity and negative predictive value were 93 and 89% respectively. Conclusion: EH has the potential to be served as an imaging biomarker to predict LVI in breast cancer especially for tumors ≤ 2 cm. Advances in knowledge: There was no association between LVI and other most commonly used elastic features such as SWVmean and SWVmax. Elastic heterogeneity is an independent predictor of LVI, so it can provide additional prognostic information for routine preoperative breast cancer assessment. For tumors ≤ 2cm, using EH value higher than 1.36 m/s to predict LVI involvement, the sensitivity and negative predictive value can reach to 93% and 89%, respectively, suggesting that breast cancer with negative EH value was more likely to be absent of LVI.

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