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Molecular biology and breast cancer

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https://www.readbyqxmd.com/read/28625363/design-synthesis-and-biological-evaluation-of-novel-indolin-2-ones-as-potent-anticancer-compounds
#1
Andong Zhou, Lei Yan, Fangfang Lai, Xiaoguang Chen, Masuo Goto, Kuo-Hsiung Lee, Zhiyan Xiao
The indolin-2-one core is a privileged structure for antitumor agents, especially kinase inhibitors. Twenty-three novel indolin-2-ones were designed by molecular dissection of the anticancer drug indirubin. Seventeen of them exhibited significant inhibition against the tested cell lines, and two of them (1c and 1h) showed IC50 values at the submicromolar level against HCT-116 cells. Compounds 1c and 2c were also potent inhibitors of the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometry was utilized to explore the antitumor mechanism of 1c and 2c with MDA-MB-231 cells, and distinct effects were observed on 2c...
June 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28623955/precision-medicine-in-breast-cancer-reality-or-utopia
#2
REVIEW
Ali Bettaieb, Catherine Paul, Stéphanie Plenchette, Jingxuan Shan, Lotfi Chouchane, François Ghiringhelli
Many cancers, including breast cancer, have demonstrated prognosis and support advantages thanks to the discovery of targeted therapies. The advent of these new approaches marked the rise of precision medicine, which leads to improve the diagnosis, prognosis and treatment of cancer. Precision medicine takes into account the molecular and biological specificities of the patient and their tumors that will influence the treatment determined by physicians. This new era of medicine is accessible through molecular genetics platforms, the development of high-speed sequencers and means of analysis of these data...
June 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28623731/new-cu-ii-complexes-with-pyrazolyl-derived-schiff-base-ligands-synthesis-and-biological-evaluation
#3
Nádia Ribeiro, Somnath Roy, Nataliya Butenko, Isabel Cavaco, Teresa Pinheiro, Irina Alho, Fernanda Marques, Fernando Avecilla, João Costa Pessoa, Isabel Correia
Since the discovery of cisplatin there has been a continuous pursuit for new metallodrugs showing higher efficacies and lower side effects. In this work, new copper(II) complexes (C1-C6) of Schiff bases derived from pyrazolyl were developed. Through condensation of 5-methyl-1H-pyrazole-3-carbohydrazide with different aromatic aldehydes - pyridoxal, salicylaldehyde, 3-methoxy-2-hydroxybenzaldehyde, 3-ethoxy-2-hydroxybenzaldehyde and 2-hydroxynaphthene-1-carbaldehyde - a set of new pyrazole based "ONO" tridentate Schiff bases were obtained in moderate to good yields - L1-L6, as well as their Cu(II)-complexes...
June 1, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28620137/biological-specificity-of-cdk4-6-inhibitors-dose-response-relationship-in-vivo-signaling-and-composite-response-signature
#4
Erik S Knudsen, Jack Hutcheson, Paris Vail, Agnieszka K Witkiewicz
Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner...
June 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618951/biological-evaluation-of-octahydropyrazin-2-1-a-5-4-a-diisoquinoline-derivatives-as-potent-anticancer-agents
#5
Agnieszka Gornowicz, Natalia Pawłowska, Anna Czajkowska, Robert Czarnomysy, Anna Bielawska, Krzysztof Bielawski, Olga Michalak, Olga Staszewska-Krajewska, Zbigniew Kałuża
In this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives (1-7) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to determine apoptosis. The activity of caspases 3, 8, 9, and 10 was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The results from experiments were compared with effects obtained after incubation in the presence of camptothecin and etoposide...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617341/microwave-assisted-facile-synthesis-anticancer-evaluation-and-docking-study-of-n-5-substituted-methylene-amino-1-3-4-thiadiazol-2-yl-methyl-benzamide-derivatives
#6
Shailee V Tiwari, Sumaiya Siddiqui, Julio A Seijas, M Pilar Vazquez-Tato, Aniket P Sarkate, Deepak K Lokwani, Anna Pratima G Nikalje
In the present work, 12 novel Schiff's bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel 7(a-l) N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide was carried out under microwave irradiation. Structures of the synthesized compounds were confirmed by IR, NMR, mass spectral study and elemental analysis...
June 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28616363/insights-from-global-analyses-of-long-noncoding-rnas-in-breast-cancer
#7
Andrew J Warburton, David N Boone
PURPOSE OF REVIEW: The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of lncRNAs in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer? RECENT FINDINGS: Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousands of long noncoding RNAs that are expressed and dysregulated in breast cancer...
March 2017: Current Pathobiology Reports
https://www.readbyqxmd.com/read/28615672/reconstruction-of-pathway-modification-induced-by-nicotinamide-using-multi-omic-network-analyses-in-triple-negative-breast-cancer
#8
Ji Young Kim, Hyebin Lee, Jongmin Woo, Wang Yue, Kwangsoo Kim, Seongmin Choi, Ja-June Jang, Youngsoo Kim, In Ae Park, Dohyun Han, Han Suk Ryu
Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614911/pd-l1-promotes-oct4-and-nanog-expression-in-breast-cancer-stem-cells-by-sustaining-pi3k-akt-pathway-activation
#9
Sheema Almozyan, Dilek Colak, Fatmah Mansour, Ayodele Alaiya, Olfat Al-Harazi, Amal Qattan, Falah Al-Mohanna, Monther Al-Alwan, Hazem Ghebeh
The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance, and epithelial-to-mesenchymal transition (EMT); all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p<0...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28611537/therapeutic-advances-and-new-directions-for-triple-negative-breast-cancer
#10
REVIEW
Eleni Andreopoulou, Catherine M Kelly, Hayley M McDaid
Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely BRCA1 and 2, and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP)...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28608266/potentially-pathogenic-germline-chek2-c-319-2t-a-among-multiple-early-onset-cancer-families
#11
Mev Dominguez-Valentin, Sigve Nakken, Hélène Tubeuf, Daniel Vodak, Per Olaf Ekstrøm, Anke M Nissen, Monika Morak, Elke Holinski-Feder, Alexandra Martins, Pål Møller, Eivind Hovig
To study the potential contribution of genes other than BRCA1/2, PTEN, and TP53 to the biological and clinical characteristics of multiple early-onset cancers in Norwegian families, including early-onset breast cancer, Cowden-like and Li-Fraumeni-like syndromes (BC, CSL and LFL, respectively). The Hereditary Cancer Biobank from the Norwegian Radium Hospital was used to identify early-onset BC, CSL or LFL for whom no pathogenic variants in BRCA1/2, PTEN, or TP53 had been found in routine diagnostic DNA sequencing...
June 12, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28607444/identification-of-novel-dysregulated-key-genes-in-breast-cancer-through-high-throughput-chip-seq-data-analysis
#12
Utkarsh Raj, Imlimaong Aier, Rahul Semwal, Pritish Kumar Varadwaj
Breast cancer is the most common cancer in women both in the developed and less developed countries, and it imposes a considerable threat to human health. Therefore, in order to develop effective targeted therapies against Breast cancer, a deep understanding of its underlying molecular mechanisms is required. The application of deep transcriptional sequencing has been found to be reported to provide an efficient genomic assay to delve into the insights of the diseases and may prove to be useful in the study of Breast cancer...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601367/breast-cancer-biomarkers-at-niger-delta-university-hospital-comparisons-with-national-and-international-trends-and-clinical-significance
#13
Yibala I Oboma, Benjamin E Susan, Stephen O Elesha, Madukwe Jonathan
Breast cancer biology is heterogeneous and patients with the same diagnostic profile have markedly different clinical outcomes. Gene expression profiling and its surrogate IHC markers classified breast cancer into four molecular subtypes with different prognosis, targeted therapies, and/or clinical outcomes. The present study was conducted to investigate breast cancer subtypes among women in NDUTH Bayelsa state and compared them with similar studies in other populations of international and national origin...
June 3, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28595943/a-role-for-g-protein-coupled-estrogen-receptor-gper-in-estrogen-induced-carcinogenesis-dysregulated-glandular-homeostasis-survival-and-metastasis
#14
REVIEW
Edward J Filardo
Mechanisms of carcinogenesis by estrogen center on its mitogenic and genotoxic potential on tumor target cells. These models suggest that estrogen receptor (ER) signaling promotes expansion of the transformed population and that subsequent accumulation of somatic mutations that drive cancer progression occur via metabolic activation of cathecol estrogens or by epigenetic mechanisms. Recent findings that GPER is linked to obesity, vascular pathology and immunosuppression, key events in the development of metabolic syndrome and intra-tissular estrogen synthesis, provides an alternate view of estrogen-induced carcinogenesis...
June 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28591735/discoidin-domain-receptor-1-modulates-insulin-receptor-signaling-and-biological-responses-in-breast-cancer-cells
#15
Veronica Vella, Roberta Malaguarnera, Maria Luisa Nicolosi, Chiara Palladino, Cristina Spoleti, Michele Massimino, Paolo Vigneri, Michele Purrello, Marco Ragusa, Andrea Morrione, Antonino Belfiore
The fetal isoform A of the insulin receptor (IR-A) is frequently overexpressed in a variety of malignancies including breast cancer. IR overexpression has a recognized role in cancer progression and resistance to anticancer therapies. In particular, IR-A has a peculiar mitogenic potential and is activated not only by insulin but also by IGF-2. Previously, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591378/is-there-a-role-for-voltage-gated-na-channels-in-the-aggressiveness-of-breast-cancer
#16
P Rhana, R R Trivelato, P S L Beirão, J S Cruz, A L P Rodrigues
Breast cancer is the most common cancer among women and its metastatic potential is responsible for numerous deaths. Thus, the need to find new targets for improving treatment, and even finding the cure, becomes increasingly greater. Ion channels are known to participate in several physiological functions, such as muscle contraction, cell volume regulation, immune response and cell proliferation. In breast cancer, different types of ion channels have been associated with tumorigenesis. Recently, voltage-gated Na+ channels (VGSC) have been implicated in the processes that lead to increased tumor aggressiveness...
June 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28583434/27-hydroxycholesterol-a-novel-player-in-molecular-carcinogenesis-of-breast-and-prostate-cancer
#17
REVIEW
Gurdeep Marwarha, Shaneabbas Raza, Kimberly Hammer, Othman Ghribi
Several studies have suggested an etiological role for hypercholesterolemia in the pathogenesis of breast cancer and prostate cancer (PCa). However, the molecular mechanisms that underlie and mediate the hypercholesterolemia-fostered increased risk for breast cancer and PCa are yet to be determined. The discovery that the most abundant cholesterol oxidized metabolite in the plasma, 27 hydroxycholesterol (27-OHC), is a selective estrogen receptor modulator (SERM) and an agonist of Liver X receptors (LXR) partially fills the void in our understanding and knowledge of the mechanisms that may link hypercholesterolemia to development and progression of breast cancer and PCa...
June 2, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28583138/molecular-characterization-of-breast-cancer-cell-lines-through-multiple-omic-approaches
#18
Shari E Smith, Paul Mellor, Alison K Ward, Stephanie Kendall, Megan McDonald, Frederick S Vizeacoumar, Franco J Vizeacoumar, Scott Napper, Deborah H Anderson
BACKGROUND: Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated...
June 5, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28581196/phytochemical-study-of-the-genus-salpichroa-solanaceae-chemotaxonomic-considerations-and-biological-evaluation-in-prostate-and-breast-cancer-cells
#19
Ana Valentina Basso, Segundo Leiva González, Gloria Estela Barboza, Valeria Pilar Careaga, Juan Carlos Calvo, Paula A Sacca, Viviana Estela Nicotra
Twelve Salpichroa taxa have been phytochemically analyzed. From the aerial parts of S. scandens, the four known salpichrolides A, C, I, S, and an unreported withanolide named salpichrolide V (1), were isolated. In S. dependens, S. gayi, S. glandulosa subsp. glandulosa, S. glandulosa subps. weddellii, S. leucantha, S. micrantha, S. microloba, S. proboscidea, S. ramosissima, S. tristis var. tristis, and S. weberbauerii, no withanolides were found. The chemical content of ca. 85 % of the Salpichroa taxa is in agreement with molecular studies, which suggest that Salpichroa and Jaborosa, a genus considered morphologically close to Salpichroa, are distant in the systematic of the Solanoideae subfamily...
June 5, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28580868/cell-cycle-therapeutics-come-of-age
#20
Matthew Ingham, Gary K Schwartz
The ability to sustain unscheduled proliferation is a hallmark of cancer. The normal process of cell division occurs via the cell cycle, a series of highly regulated steps that are orchestrated at the molecular level by specific cyclins that act in association with cyclin-dependent kinases (CDKs). Cyclin D and CDK4/6 play a key role in cell-cycle progression by phosphorylating and inactivating the retinoblastoma protein, a tumor suppressor that restrains G1- to S-phase progression. The first-generation CDK inhibitors demonstrated broad activity upon several CDKs, which likely explains their considerable toxicities and limited efficacy...
June 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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