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RNA sequencing Breast Cancer

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https://www.readbyqxmd.com/read/29156805/circulating-tumor-dna-shows-variable-clonal-response-of-breast-cancer-during-neoadjuvant-chemotherapy
#1
Ji-Yeon Kim, Donghyun Park, Dae-Soon Son, Seok Jin Nam, Seok Won Kim, Hae Hyun Jung, Yeon Jeong Kim, Gahee Park, Woong-Yang Park, Jeong Eon Lee, Yeon Hee Park
Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1(st) cycle of NAC and after curative surgery...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#2
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29139094/investigating-the-therapeutic-potential-and-mechanism-of-curcumin-in-breast-cancer-based-on-rna-sequencing-and-bioinformatics-analysis
#3
Rong Wang, Jinbin Li, Yulan Zhao, Yapeng Li, Ling Yin
BACKGROUND: Breast cancer is a prevalent cancer in female. This study aims to investigate the therapeutic potential and mechanism of curcumin in breast cancer. METHODS: After cultivation, human breast cancer cells (MCF-7 cells) were treated with 0.1% (v/v) 15 µmol/ml curcumin-dimethylsulfoxide solution and 0.1% (v/v) dimethylsulfoxide, respectively, at 37 °C and 5% CO2 for 48 h. Total RNA was extracted, cDNA library was constructed, and cDNAs were amplified and sequenced...
November 14, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29138205/long-term-prognosis-of-young-breast-cancer-patients-%C3%A2-40-years-who-did-not-receive-adjuvant-systemic-treatment-protocol-for-the-paradigm-initiative-cohort-study
#4
Gwen Mhe Dackus, Natalie D Ter Hoeve, Mark Opdam, Willem Vreuls, Zsuzsanna Varga, Esther Koop, Stefan M Willems, Carolien Hm Van Deurzen, Emilie J Groen, Alicia Cordoba, Jos Bart, Antien L Mooyaart, Jan G van den Tweel, Vicky Zolota, Jelle Wesseling, Anna Sapino, Ewa Chmielik, Ales Ryska, Frederic Amant, Annegien Broeks, Ron Kerkhoven, Nikolas Stathonikos, Mitko Veta, Adri Voogd, Katarzyna Jozwiak, Michael Hauptmann, Marlous Hoogstraat, Marjanka K Schmidt, Gabe Sonke, Elsken van der Wall, Sabine Siesling, Paul J van Diest, Sabine C Linn
INTRODUCTION: Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative...
November 14, 2017: BMJ Open
https://www.readbyqxmd.com/read/29136926/simple-g-quadruplex-based-2-aminopurine-fluorescence-probe-for-highly-sensitive-and-amplified-detection-of-microrna-21
#5
Shiyu Li, Chan Liu, Hang Gong, Chunyan Chen, Xiaoming Chen, Changqun Cai
Based on 2-aminopurine (2-AP) probe in conjunction with a G-quadruplex structure and signal amplification technique, a simple and highly sensitive fluorescence sensor for detecting microRNA (miRNA) is developed for high signal-to-background ratio and wide linear range. The proposed sensor contains two hairpins DNA: H1 and H2. H1 is labeled by 2-AP incorporated into a G-rich sequence. Upon the addition of a target miRNA, H1 is unfolded and forms DNA/RNA complexes that contain a G-quadruplex, thereby significantly enhancing 2-AP fluorescence due to the protection provided by the G-quadruplex...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29135975/transcriptomic-profiling-of-human-breast-and-melanoma-cells-selected-by-migration-through-narrow-constraints
#6
Dominika A Rudzka, William Clark, Ann Hedley, Gabriela Kalna, Michael F Olson
The metastatic spread of cancer cells is a step-wise process that starts with dissociation from primary tumours and local invasion of adjacent tissues. The ability to invade local tissues is the product of several processes, including degradation of extracellular matrices (ECM) and movement of tumour cells through physically-restricting gaps. To identify properties contributing to tumour cells squeezing through narrow gaps, invasive MDA-MB-231 human breast cancer and MDA-MB-435 human melanoma cells were subjected to three successive rounds of selection using cell culture inserts with highly constraining 3 μm pores...
November 14, 2017: Scientific Data
https://www.readbyqxmd.com/read/29131211/pharmaco-genomic-investigations-of-organo-iridium-anticancer-complexes-reveal-novel-mechanism-of-action
#7
Jessica M Hearn, George M Hughes, Isolda Romero-Canelón, Alison F Munro, Belén Rubio-Ruiz, Zhe Liu, Neil O Carragher, Peter J Sadler
Resistance to platinum drugs (used in >50% of cancer chemotherapies) is a clinical problem. Other precious metal complexes with distinct mechanisms of action might overcome this. Half-sandwich organometallic complexes containing arene or cyclopentadienyl (Cp) ligands show promise. We screened two iridium(iii) complexes [Ir(Cp(Xbiph))(ppy)Cl] (ZL49, 1, ppy = phenylpyridine) and [Ir(Cp(Xph))(azpyNMe2)Cl]PF6 (ZL109, 2, azpyNMe2 = N,N-dimethylphenylazopyridine) in 916 cancer cell lines from 28 tissue types. On average, complex 2 was 78× more potent than 1, 36× more active than cisplatin (CDDP), and strongly active (nanomolar) in patient-derived ovarian cancer cell lines...
November 13, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29123410/long-noncoding-rna-and-mrna-profiling-in-mda-mb-231-cells-following-rnai-mediated-knockdown-of-sirt7
#8
Kun-Lin Chen, Lian Li, Yi-Ru Wang, Cheng-Min Li, Tarig Mohammed Badri, Gen-Lin Wang
Breast cancer is one of the most common malignant cancers among women and a major clinical obstacle. Although studies have reported the abnormal expression of SIRT7 in breast cancer, whether the function of SIRT7 regulates the expression of long noncoding RNAs (lncRNAs) in breast cancer remains unknown. We aimed to determine the differential expressions of mRNAs and lncRNAs associated with SIRT7 and understand the regulatory mechanism of SIRT7 in breast cancer. RNA sequencing was performed to explore the transcriptome in MDA-MB-231 cells after SIRT7 depletion, and a total of 50,634 different transcripts were identified...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29123100/dna-methylation-at-enhancers-identifies-distinct-breast-cancer-lineages
#9
Thomas Fleischer, Xavier Tekpli, Anthony Mathelier, Shixiong Wang, Daniel Nebdal, Hari P Dhakal, Kristine Kleivi Sahlberg, Ellen Schlichting, Anne-Lise Børresen-Dale, Elin Borgen, Bjørn Naume, Ragnhild Eskeland, Arnoldo Frigessi, Jörg Tost, Antoni Hurtado, Vessela N Kristensen
Breast cancers exhibit genome-wide aberrant DNA methylation patterns. To investigate how these affect the transcriptome and which changes are linked to transformation or progression, we apply genome-wide expression-methylation quantitative trait loci (emQTL) analysis between DNA methylation and gene expression. On a whole genome scale, in cis and in trans, DNA methylation and gene expression have remarkably and reproducibly conserved patterns of association in three breast cancer cohorts (n = 104, n = 253 and n = 277)...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29115931/guanylate-binding-protein-1-is-a-potential-new-therapeutic-target-for-triple-negative-breast-cancer
#10
Melissa Quintero, Douglas Adamoski, Larissa Menezes Dos Reis, Carolline Fernanda Rodrigues Ascenção, Krishina Ratna Sousa de Oliveira, Kaliandra de Almeida Gonçalves, Marília Meira Dias, Marcelo Falsarella Carazzolle, Sandra Martha Gomes Dias
BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression (ESR and PGR, respectively) and an absence of human epithelial growth factor receptor (ERBB2) amplification. Approximately 15-20% of breast malignancies are TNBC. Patients with TNBC often have an unfavorable prognosis. In addition, TNBC represents an important clinical challenge since it does not respond to hormone therapy. METHODS: In this work, we integrated high-throughput mRNA sequencing (RNA-Seq) data from normal and tumor tissues (obtained from The Cancer Genome Atlas, TCGA) and cell lines obtained through in-house sequencing or available from the Gene Expression Omnibus (GEO) to generate a unified list of differentially expressed (DE) genes...
November 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29113226/silencing-of-semaphorin-3c-suppresses-cell-proliferation-and-migration-in-mcf-7-breast-cancer-cells
#11
Xiaofang Zhu, Xiangjian Zhang, Zhiqiang Ye, Yizuo Chen, Lin Lv, Xiaohua Zhang, Hongye Hu
Previous studies have suggested that semaphorin 3C (SEMA3C) is involved in the tumorigenesis and metastasis of a number of types of cancer. The aim of the present study was to investigate the role of SEMA3C in the proliferation and migration of MCF-7 breast cancer cells. Small interfering (si)RNA sequences targeting SEMA3C were constructed and transfected into MCF-7 cells in order to silence the expression of SEMA3C. Cell proliferation and migration were measured using CCK-8 and Transwell assays, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100386/hypomethylation-associated-enhanced-transcription-of-trefoil-factor-3-mediates-tamoxifen-stimulated-oncogenicity-of-er-endometrial-carcinoma-cells
#12
Vijay Pandey, Min Zhang, Qing-Yun Chong, Mingliang You, Ainiah Rushdiana Raquib, Amit K Pandey, Dong-Xu Liu, Liang Liu, Lan Ma, Sudhakar Jha, Zheng-Sheng Wu, Tao Zhu, Peter E Lobie
Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 (TFF3), in oestrogen receptor-positive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100376/sharpin-stabilizes-estrogen-receptor-%C3%AE-and-promotes-breast-cancer-cell-proliferation
#13
Ting Zhuang, Sifan Yu, Lichen Zhang, Huijie Yang, Xin Li, Yingxiang Hou, Zhenhua Liu, Yuanyuan Shi, Weilong Wang, Na Yu, Anqi Li, Xuefeng Li, Xiumin Li, Gang Niu, Juntao Xu, Muhammad Sharif Hasni, Kun Mu, Hui Wang, Jian Zhu
Estrogen receptor α is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ERα signaling. SHARPIN is highly expressed in human breast cancer and correlates with ERα protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ERα positive breast cancer patients. SHARPIN depletion based RNA-sequence data shows that ERα signaling is a potential SHARPIN target...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#14
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29096160/mmtv-does-not-encode-viral-micrornas-but-alters-the-levels-of-cancer-associated-host-micrornas
#15
Rodney P Kincaid, Neena G Panicker, Mary M Lozano, Christopher S Sullivan, Jaquelin P Dudley, Farah Mustafa
Mouse mammary tumor virus (MMTV) induces breast cancer in mice in the absence of known virally-encoded oncogenes. Tumorigenesis by MMTV is thought to occur primarily through insertional mutagenesis, leading to the activation of cellular proto-oncogenes and outgrowth of selected cells. Here we investigated whether MMTV encodes microRNAs (miRNAs) and/or modulates host miRNAs that could contribute to tumorigenesis. High throughput small RNA sequencing analysis of MMTV-infected cells and MMTV-induced mammary tumors demonstrates that MMTV does not encode miRNAs...
October 30, 2017: Virology
https://www.readbyqxmd.com/read/29093439/combating-subclonal-evolution-of-resistant-cancer-phenotypes
#16
Samuel W Brady, Jasmine A McQuerry, Yi Qiao, Stephen R Piccolo, Gajendra Shrestha, David F Jenkins, Ryan M Layer, Brent S Pedersen, Ryan H Miller, Amanda Esch, Sara R Selitsky, Joel S Parker, Layla A Anderson, Brian K Dalley, Rachel E Factor, Chakravarthy B Reddy, Jonathan P Boltax, Dean Y Li, Philip J Moos, Joe W Gray, Laura M Heiser, Saundra S Buys, Adam L Cohen, W Evan Johnson, Aaron R Quinlan, Gabor Marth, Theresa L Werner, Andrea H Bild
Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29091754/a-targetable-egfr-dependent-tumor-initiating-program-in-breast-cancer
#17
Paul Savage, Alexis Blanchet-Cohen, Timothée Revil, Dunarel Badescu, Sadiq M I Saleh, Yu-Chang Wang, Dongmei Zuo, Leah Liu, Nicholas R Bertos, Valentina Munoz-Ramos, Mark Basik, Kevin Petrecca, Jamil Asselah, Sarkis Meterissian, Marie-Christine Guiot, Atilla Omeroglu, Claudia L Kleinman, Morag Park, Jiannis Ragoussis
Therapies targeting epidermal growth factor receptor (EGFR) have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29091292/functional-snp-in-microrna-491-5p-binding-site-of-mmp9-3-utr-affects-cancer-susceptibility
#18
Homeira Javadi Pirooz, Niloofar Jafari, Mozhdeh Rastegari, Mehrnoosh Fathi-Roudsari, Nooshin Tasharrofi, Gelareh Shokri, Hosein Sazgar, Fatemeh Kouhkan
MicroRNAs (miRNA) are small RNA molecules that negatively regulate gene expression through base pairing interactions between 3'-UTR of the target mRNAs and seed sequence of miRNA. Any changes in the recognition site could destroy binding sites or modify binding affinity, resulting in evasion from miRNA regulation. A putative binding site for miR-491-5p resides in 3'-UTR of MMP9, and a genetic variant (rs1056628 A→C) is present in this region. The role of MMP9 over expression well marked in various cancers...
November 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29079660/dual-mtor-kinases-mln0128-inhibitor-sensitizes-hr-her2-breast-cancer-patient-derived-xenografts-to-trastuzumab-or-fulvestrant
#19
Pei-Yin Hsu, Victoria Shang Wu, Noriko Kanaya, Karineh Petrossian, Hang-Kai Hsu, Duc Nguyen, Daniel Schmolze, Masaya Kai, Chun-Yu Liu, Hannah Lu, Peiguo Chu, Courtney A Vito, Laura Kruper, Joanne Mortimer, Shiuan Chen
PURPOSE: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized. EXPERIMENTAL DESIGN: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis...
October 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29066719/gene-isoforms-as-expression-based-biomarkers-predictive-of-drug-response-in-vitro
#20
Zhaleh Safikhani, Petr Smirnov, Kelsie L Thu, Jennifer Silvester, Nehme El-Hachem, Rene Quevedo, Mathieu Lupien, Tak W Mak, David Cescon, Benjamin Haibe-Kains
Next-generation sequencing technologies have recently been used in pharmacogenomic studies to characterize large panels of cancer cell lines at the genomic and transcriptomic levels. Among these technologies, RNA-sequencing enable profiling of alternatively spliced transcripts. Given the high frequency of mRNA splicing in cancers, linking this feature to drug response will open new avenues of research in biomarker discovery. To identify robust transcriptomic biomarkers for drug response across studies, we develop a meta-analytical framework combining the pharmacological data from two large-scale drug screening datasets...
October 24, 2017: Nature Communications
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