Characterized the diversity of ABCB1 subtypes in immunogenomic landscape for predicting the drug response in breast cancer

Methods ◽  
2022 ◽  
Author(s):  
Meng Chi ◽  
Qilemuge Xi ◽  
Dongqing Su ◽  
Hanshuang Li ◽  
Na Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Response

scholarly journals A 3D Bioprinted Material That Recapitulates the Perivascular Bone Marrow Structure for Sustained Hematopoietic and Cancer Models

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 480
Author(s):  
Caitlyn A. Moore ◽  
Zain Siddiqui ◽  
Griffin J. Carney ◽  
Yahaira Naaldijk ◽  
Khadidiatou Guiro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Translational Medicine ◽  
Drug Response ◽  
Drug Approval ◽  
3D Models ◽  
3D Bioprinting ◽  
Effective Evaluation ◽  
Experimental Systems ◽  
Cancer Models

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ, making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M): alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various diseases and also for drug screening.

scholarly journals Clinical Identification of Dysregulated Circulating microRNAs and Their Implication in Drug Response in Triple Negative Breast Cancer (TNBC) by Target Gene Network and Meta-Analysis

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 549
Author(s):  
Amal Qattan ◽  
Taher Al-Tweigeri ◽  
Wafa Alkhayal ◽  
Kausar Suleman ◽  
Asma Tulbah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Drug Response ◽  
Triple Negative ◽  
Meta Analysis ◽  
Integrated Analysis ◽  
Circulating Mirnas ◽  
Persistent Problem ◽  
Network Analyses

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC.

Dihydrotestosterone induces chemo-resistance of triple-negative breast MDA-MB-231 cancer cells towards doxorubicin independent of ABCG2 and miR-328-3p

2021 ◽  
Vol 14 ◽  
Author(s):  
Bayan Al-Momany ◽  
Hana Hammad ◽  
Mamoun Ahram
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Drug Response ◽  
Therapeutic Strategy ◽  
Triple Negative ◽  
Model System ◽  
Cell Resistance ◽  
Protein Levels ◽  
Abcg2 Protein ◽  
Mcf 7

Background: Androgens potentially have an important role in the biology of breast cancer, particularly triple-negative breast cancer (TNBC). Androgen receptor (AR) may offer a novel therapeutic strategy including the use of microRNA (miRNA) molecules. We have previously shown that AR agonist, dihydrotestosterone (DHT), increases the expression of miR-328-3p in the TNBC MDA-MB-231 cells. One target of the latter miRNA is ATP-binding cassette subfamily G member 2 (ABCG2), which modulates the chemo-response of cancer cells by pumping out xenobiotics. Objective: Using MDA-MB-231 cells as a model system for TNBC, we hypothesized that DHT would induce cell sensitivity towards doxorubicin via increasing levels of miR-328-3p and, consequently, reducing ABCG2 levels. Methods: Chemo-response of cells towards doxorubicin, tamoxifen, and mitoxantrone was evaluated using cell viability MTT assay. Cells were transfected with both miR-328-3p mimic or antisense molecules. Real-time PCR was utilized to assess RNA levels and immunoblotting was performed to investigate levels of ABCG2 protein. PCR arrays were used to assess changes in the expression of drug response regulatory genes. Results: Contrary to our hypothesis, treating MDA-MB-231 cells with DHT, no effect towards tamoxifen or mitoxantrone and increased cell resistance towards doxorubicin were noted, concomitant with decreased expression of ABCG2. This under-expression of ABCG2 was also found in MCF-7 and MDA-MB-453 cells treated with DHT. Although miR-328-3p decreased ABCG2 mRNA and protein levels, the miRNA did not alter the chemo-response of cells towards doxorubicin and did not affect DHT-induced chemo-resistance. AR activation slightly decreased the expression of 5 genes, including insulin-like growth factor 1 receptor, that may explain the mechanism of DHT-induced chemo-resistance of cells. Conclusion: DHT regulates chemo-response via a mechanism independent of ABCG2 and miR-328-3p.

scholarly journals Can the Histoculture Drug Response Assay Predict the Clinical Results of Chemotherapy in Breast Cancer?

2007 ◽  
Vol 10 (3) ◽  
pp. 193 ◽  
Author(s):  
Yong Sik Jung ◽  
Young Up Cho ◽  
Young Jin Suh ◽  
Jeong Soo Kim ◽  
Se-Jeong Oh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Response ◽  
Clinical Results ◽  
Histoculture Drug Response Assay

The Role of Drug Resistance Causing lncRNAs in Breast Cancer: In-silico Analysis

2021 ◽  
Author(s):  
Amirhossein Hajialiasgary Najafabadi ◽  
Mahdieh Khojasteh ◽  
Kamran Ghaedi
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Roc Curve ◽  
Drug Response ◽  
Cox Regression ◽  
Patient Survival ◽  
Biological Pathways ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background: Breast cancer is the most common cancer in women globally. LncRNAs are non-coding RNAs that play an essential role in biological pathways. Many lncRNAs have been discovered to influence cancer medication resistance. As a result, identifying how lncRNAs may cause drug resistance is vital.Method: Breast cancer TCGA RNA-seq data was applied in this study. We used the PharmacoGX package to explore lncRNAs with drug resistance or sensitivity effect through GDSC and CCLE data. Differential gene expression analysis (DGE) was used to find dysregulated lncRNAs (P<0.01). Survival analysis was performed to identify lncRNAs associated with patient survival, and a model based on them was developed. Multivariate cox regression analysis and ROC curve analysis were applied to assess the model. The TCGA-BRCA and two independent datasets (GSE21653 and GSE20685) were used to study the relevance of lncRNAs in biological pathways. lncRNA-miRNA-mRNA interaction network was investigated. The connections of lncRNAs with MRPs were analysed through the correlation test. Finally, lncRNA and MRP mRNAs attachment sites were analysed through the LncRRisearch tool.Result: According to our data, thirty-eight lncRNAs were associated with cell drug response in breast cancer cells. IL12A-AS1, AC137723.1, LINC00667, SVIL-AS1, CYTOR, and MIR4435-2HG linked to patient survival (P<0.05). AC137723.1 and LINC00667 were identified as good prognostic genes, while the others were discovered to have poor prognostic effects. Moreover, the risk score model separated patients perfectly, in which about 45% of high-risk patients were dead; by contrast, around 95% of low-risk patients could survive. ROC curve results proved that CYTOR, MIR4435-2HG, and LINC00667 are potential biomarkers in breast cancer with AUC >0.8. Pathway analysis revealed that CYTOR and MIR4435-2HG are highly correlated with the Epithelial-Mesenchymal transition pathway, while AC137723.1 and LINC00667 were negatively correlated with the pathway. AC128688.2, CYTOR, TDRKH-AS1 and LINC00667 can participate in lncRNA-miRNA-mRNA networks. Also, MIR22HG might influence drug resistance by attaching to MRP mRNAs.Conclusion: Our findings revealed 38 lncRNAs involved in cancer cell treatment resistance and sensitivity. They can participate in patients’ prognosis, diagnosis and cellular pathways. Also, they may influence cell drug response through connections with CSPs, lncRNA-miRNA-mRNA networks and MRPs.

Abstract B201: Drug response profiling, redox ratio, and biomarker analysis in an in vitro 3D tri-culture model of breast cancer

2015 ◽  
Author(s):  
Tessa DesRochers ◽  
Stephen Shuford ◽  
Christina Mattingly ◽  
Terri Bruce ◽  
Matt Gevaert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Response ◽  
Redox Ratio ◽  
Culture Model ◽  
Biomarker Analysis

scholarly journals Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer

2014 ◽  
Vol 74 (18) ◽  
pp. 5184-5194 ◽  
Author(s):  
Alex J. Walsh ◽  
Rebecca S. Cook ◽  
Melinda E. Sanders ◽  
Luigi Aurisicchio ◽  
Gennaro Ciliberto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Optical Imaging ◽  
Primary Tumor ◽  
Drug Response

Molecular classification with NanoString nCounter system in triple-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23198-e23198
Author(s):  
Sung Gwe Ahn ◽  
Seung Joon Kim ◽  
Hak Woo Lee ◽  
Hyo Jeong Yoon ◽  
Chungyeul Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Drug Response ◽  
Triple Negative ◽  
Molecular Classification ◽  
Severance Hospital ◽  
Brca1 Promoter Methylation ◽  
Pearson's R ◽  
Pearson’S R

e23198 Background: Previous studies have shown that several distinct subtypes identified by gene expression profiling (GEP) consisted of triple-negative breast cancer (TNBC). Compared with the subtypes defined by GEP, we developed molecular classification with NanoString nCounter system in TNBC. Methods: GEP was conducted on 188 FFPE containing chemotherapy-naïve TNBC tumors collected at Gangnam Severance Hospital. To select core genes for classification, other 120 samples from public GEP database were used. Correlation between nCounter system and GEP using identical RNA was done. In a part of tumors, BRCA1 methylation, homologous recombination deficiency (HRD) assay, and drug response assay with ATP was comprehensively assessed. Results: To classify TNBC into 4 major subtypes (Basal-like: BL, Luminal androgen receptor: LAR, Mesenchymal: M, and Immune-modulatory: IM) according to the Vanderbilt classification, we selected 110 genes in 220 samples with GEP (100 from Gangnam Severance Hospital and 120 from public database). In other 88 samples, the classification with the 110 genes were validated. In 149 tumors excluding UNS subtype by the Vanderbilt, a correlation between 110 genes-classification and the Vanderbilt system was 74.4% (111 of 149, Pearson’s R = 0.726). In 180 tumors with GEP and nCounter assay, a correlation between them was 85.0% (153 of 180, Pearson’s R = 0.827). Compared with tumors of the IM type by 110-genes, the recurrence-free survival was significantly reduced in tumors of the non-IM type by 110-genes ( P= 0.049). In cases with BRCA1 methylation test (n = 147), a significant higher rate of BRCA1 promoter methylation was found in BL type by nCounter system (BL: 41.0% vs. non-BL: 19.4%). In cases with HRD test, a significant lower rate of HRD was found in nCounter-identified LAR type (LAR: 0% vs. non-LAR: 79.3%). In patients with in vitro drug response assay with cisplatin (n = 36), tumors with nCounter-BL had a significant higher responsiveness than tumors with others ( P= 0.028). Conclusions: Our work shows the feasibility of molecular classification with nCounter system in TNBC. Future study warrants the clinical utility of this classification to guide the subtype-specific therapy in patients with TNBC.

The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients

2015 ◽  
Vol 129 (9) ◽  
pp. 809-822 ◽  
Author(s):  
Miao He ◽  
Yingzi Fu ◽  
Yuanyuan Yan ◽  
Qinghuan Xiao ◽  
Huizhe Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Human Breast Cancer ◽  
Drug Response ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Hedgehog Signalling ◽  
Hedgehog Signalling Pathway ◽  
Xenograft Mice ◽  
Mcf 7

Our study showed that Hh signalling activation contributed to BCSC-mediated chemoresistance in cultured breast cancer MCF-7 MS cells, in xenograft mice and in human breast cancer patients.

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