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https://www.readbyqxmd.com/read/28446749/dynamics-of-chromatin-accessibility-during-tgf-%C3%AE-induced-emt-of-ras-transformed-mammary-gland-epithelial-cells
#1
Mayu Arase, Yusuke Tamura, Natsumi Kawasaki, Kazunobu Isogaya, Ryo Nakaki, Anna Mizutani, Shuichi Tsutsumi, Hiroyuki Aburatani, Kohei Miyazono, Daizo Koinuma
Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-β and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing. TGF-β and Ras altered chromatin accessibility either cooperatively or independently, and AP1, ETS, and RUNX binding motifs were enriched in the accessible chromatin regions of EpH4 and EpRas cells...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#2
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28446206/cooperation-of-neurotrophin-receptor-trkb-and-her2-in-breast-cancer-cells-facilitates-brain-metastases
#3
Cecilia Choy, Khairul I Ansari, Josh Neman, Sarah Hsu, Matthew J Duenas, Hubert Li, Nagarajan Vaidehi, Rahul Jandial
BACKGROUND: Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. The neural niche poses unique selection pressures, and neoplastic cells that utilize the brain microenvironment may have a survival advantage...
April 26, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#4
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443499/high-expression-of-partitioning-defective-3-like-protein-is-associated-with-malignancy-in-colorectal-cancer
#5
Taiyuan Li, Xiaoyang Liu, Qunguang Jiang, Xiong Lei, Dongning Liu
Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442393/progesterone-receptors-pr-mediate-stat-actions-pr-and-prolactin-receptor-signaling-crosstalk-in-breast-cancer-models
#6
Katherine A Leehy, Thu H Truong, Laura J Mauro, Carol A Lange
Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy...
April 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28441888/doxorubicin-induced-female-reproductive-toxicity-an-assessment-of-ovarian-follicular-apoptosis-cyclicity-and-reproductive-tissue-histology-in-wistar-rats
#7
Kumari Nishi, Vinoth Prasanna Gunasekaran, Jaganath Arunachalam, Mathan Ganeshan
Doxorubicin is a widely used chemotherapeutic agent for various cancers, particularly for the female breast cancer patients. Although the rate of young female cancer patients is increasing every year, conversely the lack of knowledge of adverse effects of doxorubicin on female reproductive system insisted us to assess the toxic effects of doxorubicin on the female reproductive tissue histoarchitecture, cyclicity, and mammary glands in Wistar rats. The rats were divided into two groups depending on the treatment period, i...
April 25, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28439706/cks1bp7-a-pseudogene-of-cks1b-is-co-amplified-with-igf1r-in-breast-cancers
#8
Yansong Liu, Wei Wang, Yan Li, Feifei Sun, Jiaxiang Lin, Li Li
Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes...
April 24, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28438966/mediation-of-movement-induced-breakthrough-cancer-pain-by-ib4-binding-nociceptors-in-rats
#9
Joshua Havelin, Ian Imbert, Devki Sukhtankar, Bethany Remeniuk, Ian Pelletier, Jonathan Gentry, Alec Okun, Timothy Tiutan, Frank Porreca, Tamara King
Cancer-induced bone pain (CIBP) is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We previously demonstrated that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i...
April 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28438614/the-expression-of-growth-hormone-releasing-hormone-ghrh-and-its-receptors-in-breast-carcinomas-with-apocrine-differentiation-further-evidence-of-the-presence-of-a-ghrh-pathway-in-these-tumors
#10
Bence Kővári, Semir Vranic, Caterina Marchio, Anna Sapino, Gábor Cserni
Apocrine breast carcinomas were evaluated for the expression of components of the growth hormone-releasing hormone (GHRH) autocrine/paracrine pathway: GHRH and its receptors (GHRH-R), as mammary apocrine carcinomas and epithelium seemed to be uniformly positive for GHRH-R in a pilot study. The apocrine phenotype was determined on the basis of hematoxylin-eosin morphology and a congruent immunohistochemical profile (estrogen receptor negativity, androgen receptor and gross cystic disease fluid protein-15 positivity)...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28435746/the-paradoxical-functions-of-egfr-during-breast-cancer-progression
#11
Remah Ali, Michael K Wendt
The epidermal growth factor receptor (EGFR) is one of the most well-studied signaling pathways in cancer progression. As a result, numerous therapeutics including small-molecule inhibitors and monoclonal antibodies have been developed to target this critical oncogenic driver. Several of these EGFR inhibitors (EGFRi) have been evaluated in metastatic breast cancer, as high-level EGFR expression in primary tumors correlates with the highly aggressive basal-like phenotype and predicts for poor patient prognosis...
2017: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/28433771/a-versatile-tumor-gene-deletion-system-reveals-a-crucial-role-for-fgfr1-in-breast-cancer-metastasis
#12
Wei Wang, Yanling Meng, Bingning Dong, Jie Dong, Michael M Ittmann, Chad J Creighton, Lu Yang, Hong Zhang, Tao Shen, Jianghua Wang, David R Rowley, Yi Li, Fengju Chen, David D Moore, Feng Yang
RCAS avian viruses have been used to deliver oncogene expression and induce tumors in transgenic mice expressing the virus receptor TVA. Here we report the generation and characterization of a novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. FGF receptor 1 (FGFR1) is a gene that is amplified in human breast cancer, but there have been no definitive studies on its function in mammary tumorigenesis, progression, and metastasis in vivo in spontaneous tumors in mice...
April 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#13
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28431394/effect-of-salmonella-enterica-serovar-typhimurium-vnp20009-and-vnp20009-with-restored-chemotaxis-on-4t1-mouse-mammary-carcinoma-progression
#14
Sheryl L Coutermarsh-Ott, Katherine M Broadway, Birgit E Scharf, Irving C Allen
A variety of bacterial strains have been evaluated as bio-therapeutic and immunomodulatory agents to treat cancer. One such strain, Salmonella enterica serovar Typhimurium VNP20009, which is attenuated by a purine auxotrophic mutation and modified lipid A, is characterized in previous models as a safely administered, tumor colonizing agent. However, earlier work tended to use less aggressive cancer cell lines and immunocompromised animal models. Here, we investigated the safety and efficacy of VNP20009 in a highly malignant murine model of human breast cancer...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429725/estrogen-reprograms-the-activity-of-neutrophils-to-foster-protumoral-microenvironment-during-mammary-involution
#15
Hwa Hwa Chung, Yu Zuan Or, Smeeta Shrestha, Jia Tong Loh, Chew Leng Lim, Zoe Ong, Amanda Rui En Woo, I-Hsin Su, Valerie C L Lin
Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429228/magnetic-resonance-imaging-of-tumors-with-the-use-of-iron-oxide-magnetic-nanoparticles-as-a-contrast-agent
#16
A S Semkina, M A Abakumov, N F Grinenko, A A Lipengolts, N V Nukolova, V P Chekhonin
We studied the possibility of using BSA-coated magnetic iron oxide nanoparticles for magnetic resonance imaging diagnosis of C6 glioblastoma, 4T1 mammary adenocarcinoma, and RS-1 hepatic mucous carcinoma. In all three cases, magnetic nanoparticles accumulated in the tumor and its large vessels. Magnetic resonance imaging with contrast agent allows visualization of the tumor tissue and its vascularization.
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428275/epithelial-to-mesenchymal-transition-contributes-to-immunosuppression-in-breast-carcinomas
#17
Anushka Dongre, Mohammad Rashidian, Ferenc Reinhardt, Aaron Bagnato, Zuzana Keckesova, Hidde L Ploegh, Robert A Weinberg
The Epithelial-to-mesenchymal transition (EMT) is a cell-biological program that confers mesenchymal traits on carcinoma cells and drives their metastatic dissemination. It is, unclear, however, whether activation of EMT in carcinoma cells can change their susceptibility to immune attack. We demonstrate here that mammary tumor cells arising from more epithelial carcinoma cell lines expressed high levels of MHC-I, low levels of PD-L1 and contained within their stroma CD8+ T cells and M1 (anti-tumor) macrophages...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#18
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427009/early-in-life-dietary-zinc-deficiency-and-supplementation-and-mammary-tumor-development-in-adulthood-female-rats
#19
Flávia R M da Silva, Tony F Grassi, Joyce R Zapaterini, Lucas T Bidinotto, Luis F Barbisan
Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning...
April 1, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28424200/whole-exome-sequencing-of-metaplastic-breast-carcinoma-indicates-monoclonality-with-associated-ductal-carcinoma-component
#20
Bracha Avigdor, Katie Beierl, Christopher D Gocke, Daniel Zabransky, Karen Cravero, Kelly Kyker-Snowman, Berry Button, David Chu, Sarah Croessmann, Rory L Cochran, Roisin Connolly, Ben Ho Park, Ashley Cimino-Mathews, Sarah J Wheelan
Although most human cancers display a single histology, there are unusual cases where two or more distinct tissue types present within a primary tumor. One such example is metaplastic breast carcinoma, a rare but aggressive cancer with a heterogenous histology, including squamous, chondroid, and spindle cells. Metaplastic carcinomas often contain an admixed conventional ductal invasive or in situ mammary carcinoma component, and are typically triple-negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER-2) amplification/overexpression...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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