scholarly journals The Role of Long Noncoding RNAs in Patients With Luminal A Invasive Breast Ductal Carcinoma

2021 ◽  
Author(s):  
Nahal Eshghifar ◽  
Fatemeh Rouhollah ◽  
Nooshin Barikrow ◽  
Farkhondeh Pouresmaeili ◽  
Mohammad Taheri
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Ductal Carcinoma ◽  
Positive Association ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Protein Coding ◽  
Diagnostic Approaches ◽  
Breast Tissues

Abstract Breast cancer is the most common form of cancer in women around the world. The molecular mechanisms of this heterogeneous disease have been extensively investigated; but still; need many sensitive and specific markers for prognostic and early diagnostic approaches. Non-protein coding RNAs known as lncRNAs are reported in tumorogenesis involvement. hence could be used as therapeutic targets.In the present study, we examined the expression levels of CCAT1, PDCD4, PDCD4-AS1, and MEG3 LncRNAs in tumor and adjacent breast tissues in 88 Iranian patients by quantitative real-time PCR. CCAT1 was notably overexpressed and PDCD4-AS1 was decreased in tumor samples, PDCD4 and PDCD4-AS1 showed a positive association with each other, higher levels of PDCD4-AS1 were associated with better survival, tumor samples showed lower levels of PDCD4 compared to normal tissue.Our findings show that lncRNAs play critical roles in controlling post-transcriptional gene expression of key tumor suppressor or oncogenic genes, leading to TNBC progression.As a result, this research looked into the prognostic role of lncRNAs in breast cancer patients.

scholarly journals Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

2019 ◽  
Vol 70 (7) ◽  
pp. 2671-2676
Author(s):  
Adriana Andreea Jitariu ◽  
Amalia Raluca Ceausu ◽  
Adriana Meche ◽  
Cristian Nica ◽  
Amelia Burlea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Microvessel Density ◽  
Ductal Carcinoma ◽  
Hot Spot ◽  
Histopathological Diagnosis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Mean Values

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

scholarly journals ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Qiushi Lin ◽  
Xuesong Chen ◽  
Fanzheng Meng ◽  
Kosuke Ogawa ◽  
Min Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Normal Adult ◽  
Luciferase Reporter ◽  
Breast Cancer Patients ◽  
Long Distance ◽  
Premetastatic Niche

Abstract Background Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer. Methods Stable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied. Results Through physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH’s β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis. Conclusions ASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH’s pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.

scholarly journals The Role of Chemotherapy in Patients With HER2-Negative Isolated Locoregional Recurrence of Breast Cancer: A Multicenter Retrospective Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Kyoungmin Lee ◽  
Sung Hoon Sim ◽  
Eun Joo Kang ◽  
Jae Hong Seo ◽  
Heejung Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Molecular Subtypes ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Prior Chemotherapy ◽  
Luminal B ◽  
Disease Free

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) <5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.

scholarly journals Model-based in silico analysis of the PI3K/Akt pathway: the elucidation of cross-talk between diabetes and breast cancer

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5917 ◽  
Author(s):  
Sammia Rehman ◽  
Ayesha Obaid ◽  
Anam Naz ◽  
Amjad Ali ◽  
Shahzina Kanwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Insulin Signaling ◽  
In Silico ◽  
In Silico Analysis ◽  
Positive Association ◽  
Pi3k Pathway ◽  
Diabetic Patients ◽  
Breast Cancer Patients

Background A positive association between diabetes and breast cancer has been identified by various epidemiological and clinical studies. However, the possible molecular interactions between the two heterogeneous diseases have not been fully determined yet. There are several underlying mechanisms which may increase the risk of breast cancer in diabetic patients. Introduction In this study, we focused on the role of O-GlcNAc transferase (OGT) enzyme in the regulation of phosphatidylinositol-3 kinase (PI3K) pathway through activation/deactivation of Akt protein. The efficiency of insulin signaling in adipocytes is reduced as a result of OGT overexpression which further attenuates Akt signaling; as a result, the efficiency of insulin signaling is reduced by downregulation of insulin-responsive genes. On the other hand, increased expression of OGT results in Akt activation in breast cancer cells, leading to enhanced cell proliferation and inhibition of the apoptosis. However, the interplay amongst these signaling pathways is still under investigation. Methods In this study, we used Petri nets (PNs) to model and investigate the role of PI3K and OGT pathways, acting as key players in crosstalk between diabetes and breast cancer, resulting in progression of these chronic diseases. Moreover, in silico perturbation experiments were applied on the model to analyze the effects of anti-cancer agents (shRNA and BZX) and anti-diabetic drug (Metformin) on the system. Results Our PN model reflects the alterations in protein expression and behavior and the correlation between breast cancer and diabetes. The analysis proposed two combination therapies to combat breast cancer progression in diabetic patients including combination of OGTmRNA silencing and OGT inhibitor (BZX) as first combination and BZX and Metformin as the second. Conclusion The PN model verified that alterations in O-GlcNAc signaling affect both insulin resistance and breast cancer. Moreover, the combination therapy for breast cancer patients consisting of anti-diabetic drugs such as Metformin along with OGT inhibitors, for example BZX, can produce better treatment regimens.

scholarly journals Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255243
Author(s):  
Fayyaz Ahmed ◽  
Muhammad Adnan ◽  
Ayesha Malik ◽  
Somayya Tariq ◽  
Farukh Kamal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Ductal Carcinoma ◽  
Clinical Samples ◽  
Lactation Period ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Data Set

Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient’s data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients’ biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.

scholarly journals The Role of Postoperative Radiotherapy After Primary Tumor Resection in Patients With De Novo Stage Iv Breast Cancer

2020 ◽  
Author(s):  
Yeon Joo Kim ◽  
Su Ssan Kim ◽  
Seung Do Ahn ◽  
Jinhong Jung ◽  
Sei-Hyun Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
De Novo ◽  
Postoperative Radiotherapy ◽  
Tumor Resection ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Free Survival ◽  
Stage Iv Breast Cancer

Abstract Background: To investigate the role of postoperative radiotherapy (PORT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR).Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS).Results: At a median follow-up of 48.9 months (range, 3.5–183.4 months), the median OS was 54.9 months (range, 5.3–185.9 months) with a 5 year OS rate of 59.6%. Luminal A or B type tumors and PORT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. PORT was the only significant predictor of LRRFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15–0.86; p = 0.021). A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. Multivariate analysis showed that PORT was significantly predictive of LRRFS (HR, 0.31; 95% CI, 0.11–0.91; p = 0.033) but not of OS. Conclusions: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT was significantly predictive of LRRFS, suggesting that patients may benefit from this treatment.Trial registration: The present study was not registered due to its retrospective nature.

scholarly journals Upregulation of miR-21 and miR-106b in plasma and tissues as a possible prognostic marker in aggressive breast cancer

2021 ◽  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Reduction Mammoplasty ◽  
Lymph Node Involvement ◽  
Normal Breast ◽  
Cancer Prognosis ◽  
Mammary Tissue ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Breast Tissues

Background: The miRNAs are referred to small non-coding RNAs (consisting of 18 to 25 nucleotides). Functional studies have shown their functions to be oncogenes or tumor suppressor genes in different types of cancers. The miR-106b and miR-21 have been identified to participate in the biological behaviors of cells. This study aimed to evaluate the tissue and plasma levels of miR-21 and miR-106b in patients with breast cancer who were diagnosed with ductal carcinoma. Methods: In total, 40 cases of breast cancer patients 180 samples were examined in this project. Samples included ductal carcinoma breast tumors (n=40), normal breast tissues of the margin of the tumor (n=40) and 20 samples from unaffected mammary tissue of females undergoing reduction mammoplasty (control group), plasma samples of patients with breast cancer (n=40), and plasma of non-affected individuals (n=40). The expression levels of miR-106b and miR-21 were determined using SYBR Green real-time RT-PCR assay in breast tissues and plasma of cancerous patients in comparison to the controls. Results: MiR-106b and miR-21 revealed much higher expression in tissues and plasma of patients with breast cancer in comparison to that in the group of control (P<0.001). High levels of mir-106b and miR-21 expression in plasma and tumor tissues were highly correlated with tumors in higher stages and lymph node involvement (P<0.0001). Conclusions: Based on the obtained results, upregulation of miR-106b and miR-21 in the plasma of patients with breast cancer can act as a possible non-invasive biomarker for breast cancer prognosis. Further follow-up studies are required to confirm this.

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