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Molecular biology and breast cancer

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https://www.readbyqxmd.com/read/28544624/pyrimidine-containing-epidermal-growth-factor-receptor-kinase-inhibitors-synthesis-and-biological-evaluation
#1
Gaurav Joshi, Himanshu Nayyar, Sourav Kalra, Praveen Sharma, Anjana Munshi, Sandeep Singh, Raj Kumar
Structure based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nM to 3 μM. mRNA expression of EGFR downstream target genes i.e. twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μM) in lung, colon and breast cancer cell lines...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544374/long-non-coding-rna-h19-promotes-the-proliferation-and-invasion-of-breast-cancer-through-upregulating-dnmt1-expression-by-sponging-mir-152
#2
Zhen Li, Yan Li, Ya Li, Kewei Ren, Xin Li, Xinwei Han, Jiaxiang Wang
Long non-coding RNA (lncRNA) H19 in tumors played important roles in various biological processes. However, the biological role and molecular mechanism of H19 in breast cancer are unclear. Here, we found that H19 was aberrantly upregulated in human breast tumor tissues and cells. A negative correlation between H19 and miR-152 and positive correlation between H19 and DNMT1 mRNA were observed. Downregulation of H19 and DNMT1 significantly retarded breast cancer cell proliferation and invasion. H19 act as an endogenous sponge by directly binding to miR-152...
May 23, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28536419/the-long-non-coding-rna-linc00152-is-essential-for-cell-cycle-progression-through-mitosis-in-hela-cells
#3
Linda Nötzold, Lukas Frank, Minakshi Gandhi, Maria Polycarpou-Schwarz, Matthias Groß, Manuel Gunkel, Nina Beil, Holger Erfle, Nathalie Harder, Karl Rohr, Jakob Trendel, Jeroen Krijgsveld, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sylvia Erhardt, Sven Diederichs
In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated in cancer entities to analyse their impact on cell division by using time-lapse microscopy. We identified 26 lncRNAs affecting cell morphology and cell cycle including LINC00152...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28531800/restoration-of-arpin-suppresses-aggressive-phenotype-of-breast-cancer-cells
#4
Yi Li, Jiliang Qiu, Ting Pang, Zhixing Guo, Yonghui Su, Qingan Zeng, Xuexia Zhang
Arpin, a negative regulator of the actin-related protein-2/3 (Arp2/3) complex, is downregulated and predicts poor prognosis in breast cancer patients. However, its biological relevance in breast cancer is still unclear. This study was conducted to investigate the roles of Arpin in breast cancer growth and invasion. We overexpressed Arpin expression in MCF-7 and MDA-MB-231 breast cancer cells and examined the effects of restoration of Arpin on cell proliferation, colony formation, cell cycle distribution, invasion in vitro and tumorigenesis in vivo...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531107/analysis-of-gene-expression-signatures-in-cancer-associated-stroma-from-canine-mammary-tumours-reveals-molecular-homology-to-human-breast-carcinomas
#5
Julia Ettlin, Elena Clementi, Parisa Amini, Alexandra Malbon, Enni Markkanen
Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526922/advances-in-systemic-therapy-for-metastatic-breast-cancer-future-perspectives
#6
REVIEW
S P Corona, N Sobhani, A Ianza, G Roviello, G Mustacchi, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28523293/-triple-positive-breast-cancer-a-novel-category
#7
George Iancu, DănuŢ Vasile, Raluca Claudia Iancu, Dragoş Virgil DaviŢoiu
Breast cancer (BC) biology is of outmost importance for its therapeutic management and for establishing patients' outcome. Breast cancer has been divided in subtypes depending on the presence of hormone receptors (HRs) for estrogen and progesterone and human epidermal growth factor receptor 2 (HER2) gene amplification. Recently, a distinct subcategory has been analyzed from the group of HER2-enriched BC with positive HR, namely HER2 positive with high levels of hormone receptor expression, suggestively named "triple positive" breast cancer...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28521431/microrna-320a-is-downregulated-in-non-small-cell-lung-cancer-and-suppresses-tumor-cell-growth-and-invasion-by-directly-targeting-insulin-like-growth-factor-1-receptor
#8
Jianguo Wang, Chunyun Shi, Jianfei Wang, Li Cao, Li Zhong, Dongmei Wang
Accumulating evidence has demonstrated that microRNAs (miRs/miRNAs) are implicated in carcinogenesis and cancer progression, and can function as oncogenes or tumor suppressor genes in human cancer types. Previous profile studies of miRNA expression levels have revealed that miR-320a was downregulated in breast cancer, colon cancer, bladder cancer, glioblastoma and salivary adenoid cystic carcinoma. However, its expression level, potential functions and the mechanisms underlying its functions in non-small cell lung cancer (NSCLC) require further investigation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#9
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28509845/metabolic-portraits-of-breast-cancer-by-hr-mas-mr-spectroscopy-of-intact-tissue-samples
#10
REVIEW
Tonje H Haukaas, Leslie R Euceda, Guro F Giskeødegård, Tone F Bathen
Despite progress in early detection and therapeutic strategies, breast cancer remains the second leading cause of cancer-related death among women globally. Due to the heterogeneity and complexity of tumor biology, breast cancer patients with similar diagnosis might have different prognosis and response to treatment. Thus, deeper understanding of individual tumor properties is necessary. Cancer cells must be able to convert nutrients to biomass while maintaining energy production, which requires reprogramming of central metabolic processes in the cells...
May 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28505536/design-synthesis-molecular-docking-and-cytotoxic-evaluation-of-novel-2-furybenzimidazoles-as-vegfr-2-inhibitors
#11
Mona A Abdullaziz, Heba T Abdel-Mohsen, Ahmed M El Kerdawy, Fatma A F Ragab, Mamdouh M Ali, Sherifa M Abu-Bakr, Adel S Girgis, Hoda I El Diwani
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21...
April 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28503860/epigenetic-silencing-of-adamts18-promotes-cell-migration-and-invasion-of-breast-cancer-through-akt-and-nf-%C3%AE%C2%BAb-signaling
#12
Hongying Xu, Qian Xiao, Yu Fan, Tingxiu Xiang, Chen Li, Chunhong Li, Shuman Li, Tianli Hui, Lu Zhang, Hongzhong Li, Lili Li, Guosheng Ren
ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70...
May 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28501990/tumor-staging-and-grading-a-primer
#13
Stacy M Telloni
Cancer staging and grading are used to predict the clinical behavior of malignancies, establish appropriate therapies, and facilitate exchange of precise information between clinicians. The internationally accepted criterion for cancer staging, the tumor-node-metastasis (TNM) system, includes: (1) tumor size and local growth (T), (2) extent of lymph node metastases (N), and (3) occurrence of distant metastases (M). Clinical stage is established before initiation of therapy and is determined by physical examination, laboratory findings, and imaging studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28495502/multipronged-quantitative-proteomics-reveals-serum-proteome-alterations-in-breast-cancer-intrinsic-subtypes
#14
Akshada Gajbhiye, Raju Dabhi, Khushman Taunk, Mashanipalya G Jagadeeshaprasad, Sourav RoyChoudhury, Anupama Mane, Santhakumari Bayatigeri, Koel Chaudhury, Manas K Santra, Srikanth Rapole
Being molecularly heterogeneous, breast cancer tends to be a complicated oncological disease with high incidence rates throughout the world. The primary aim of this study was to identify the set of serum proteins with discriminatory capabilities towards the four major subtypes of breast cancer. We employed multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS and identified 307 differentially regulated proteins. Luminal A subtype consisted of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast cancer subtype 10 differentially regulated subtype specific proteins...
May 8, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28493837/long-non-coding-rnas-may-serve-as-biomarkers-in-breast-cancer-combined-with-primary-lung-cancer
#15
Xianfeng Ding, Yuhan Zhang, Hongjian Yang, Weimin Mao, Bo Chen, Shifeng Yang, Xiaowen Ding, Dehong Zou, Wenju Mo, Xiangming He, Xiping Zhang
Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28492659/ensemble-clustering-of-phosphoproteomic-data-identifies-differences-in-protein-interactions-and-cell-cell-junction-integrity-of-her2-overexpressing-cells
#16
Katherine E Schaberg, Venktesh S Shirure, Elizabeth A Worley, Steven C George, Kristen M Naegle
Overexpression of HER2, a receptor tyrosine kinase of the ERBB family, in breast cancer is related to increased cancer progression and aggressiveness. A breast epithelial cell model with the single perturbation of HER2 overexpression is capable of replicating the increased aggressiveness of HER2 overexpressing cancers. In previous work, Wolf-Yadlin and colleagues (Wolf-Yadlin et al., Mol. Syst. Biol., 2006, 2) measured the proximal tyrosine phosphorylation dynamics of the parental and HER2 overexpressing cells (24H) in response to EGF...
May 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28483691/3d-tumor-microtissues-as-an-in-vitro-testing-platform-for-microenvironmentally-triggered-drug-delivery-systems
#17
Virginia Brancato, Filomena Gioiella, Martina Profeta, Giorgia Imparato, Daniela Guarnieri, Francesco Urciuolo, Pietro Melone, Paolo A Netti
Therapeutic approaches based on nanomedicine have garnered great attention in cancer research. In vitro biological models that better mimic in vivo conditions are crucial tools to more accurately predict their therapeutic efficacy in vivo. In this work, a new 3D breast cancer microtissue has been developed to recapitulate the complexity of the tumor microenvironment and to test its efficacy as screening platform for drug delivery systems. The proposed 3D cancer model presents human breast adenocarcinoma cells and cancer-associated fibroblasts embedded in their own ECM, thus showing several features of an in vivo tumor, such as overexpression of metallo-proteinases (MMPs)...
May 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28482874/presence-of-human-papillomavirus-dna-in-breast-cancer-a-spanish-case-control-study
#18
Silvia Delgado-García, Juan-Carlos Martínez-Escoriza, Alfonso Alba, Tina-Aurora Martín-Bayón, Hortensia Ballester-Galiana, Gloria Peiró, Pablo Caballero, Jose Ponce-Lorenzo
BACKGROUND: Breast cancer is one of the most important neoplasia among women. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). The aim of this study was to explore the presence of HPV DNA in a case-control study. METHODS: We performed our study including 251 cases (breast cancer) and 186 controls (benign breast tumors), using three different molecular techniques with PCR (GP5/GP6, CLART® and DIRECT FLOW CHIP®)...
May 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28481952/identification-of-potential-new-treatment-response-markers-and-therapeutic-targets-using-a-gaussian-process-based-method-in-lapatinib-insensitive-breast-cancer-models
#19
Tapesh Santra, Sandra Roche, Neil Conlon, Norma O'Donovan, John Crown, Robert O'Connor, Walter Kolch
Molecularly targeted therapeutics hold promise of revolutionizing treatments of advanced malignancies. However, a large number of patients do not respond to these treatments. Here, we take a systems biology approach to understand the molecular mechanisms that prevent breast cancer (BC) cells from responding to lapatinib, a dual kinase inhibitor that targets human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR). To this end, we analysed temporal gene expression profiles of four BC cell lines, two of which respond and the remaining two do not respond to lapatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28475868/glucocorticoid-receptor-megatrans-switching-mediates-the-repression-of-an-er%C3%AE-regulated-transcriptional-program
#20
Feng Yang, Qi Ma, Zhijie Liu, Wenbo Li, Yuliang Tan, Chunyu Jin, Wubin Ma, Yiren Hu, Jia Shen, Kenneth A Ohgi, Francesca Telese, Wen Liu, Michael G Rosenfeld
The molecular mechanisms underlying the opposing functions of glucocorticoid receptors (GRs) and estrogen receptor α (ERα) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ERα-activated transcriptional program by binding, in trans, to ERα-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ERα-dependent binding of components of the MegaTrans complex...
May 4, 2017: Molecular Cell
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