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https://www.readbyqxmd.com/read/29164052/development-of-novel-patient-derived-xenografts-from-breast-cancer-brain-metastases
#1
María J Contreras-Zárate, D Ryan Ormond, Austin E Gillen, Colton Hanna, Nicole L Day, Natalie J Serkova, Britta M Jacobsen, Susan M Edgerton, Ann D Thor, Virginia F Borges, Kevin O Lillehei, Michael W Graner, Peter Kabos, Diana M Cittelly
Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2(+) and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2(+) BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo, their suitability to validate therapies for established brain metastasis remains limited...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29164051/anti-inflammatory-microglia-macrophages-as-a-potential-therapeutic-target-in-brain-metastasis
#2
Kleopatra E Andreou, Manuel Sarmiento Soto, Danny Allen, Vasiliki Economopoulos, Axel de Bernardi, James R Larkin, Nicola R Sibson
Brain metastasis is a common complication of cancer patients and is associated with poor survival. Histological data from patients with brain metastases suggest that microglia are the major immune population activated around the metastatic foci. Microglia and macrophages have the ability to polarize to different phenotypes and to exert both tumorigenic and cytotoxic effects. However, the role of microglia/macrophages during the early stages of metastatic growth in the brain has not yet been determined. The aim of this study was to profile microglial/macrophage activation in a mouse model of breast cancer brain metastasis during the early stages of tumor growth, and to assess the role of the anti-inflammatory microglial/macrophage population, specifically, during this phase...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#3
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162812/role-of-epithelial-to-mesenchymal-transition-associated-genes-in-mammary-gland-regeneration-and-breast-tumorigenesis
#4
Shaheen S Sikandar, Angera H Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W Hsieh, Neethan A Lobo, Ferenc A Scheeren, Sopheak Sim, Dalong Qian, Frederick M Dirbas, George Somlo, Stephen R Quake, Michael F Clarke
Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29161592/tumor-suppressor-inactivation-of-gdf11-occurs-by-precursor-sequestration-in-triple-negative-breast-cancer
#5
Sameer S Bajikar, Chun-Chao Wang, Michael A Borten, Elizabeth J Pereira, Kristen A Atkins, Kevin A Janes
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29158484/the-hsf1-parp13-parp1-complex-facilitates-dna-repair-and-promotes-mammary-tumorigenesis
#6
Mitsuaki Fujimoto, Ryosuke Takii, Eiichi Takaki, Arpit Katiyar, Ryuichiro Nakato, Katsuhiko Shirahige, Akira Nakai
Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1-PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158396/emt-programs-promote-basal-mammary-stem-cell-and-tumor-initiating-cell-stemness-by-inducing-primary-ciliogenesis-and-hedgehog-signaling
#7
Vincent J Guen, Tony E Chavarria, Cornelia Kröger, Xin Ye, Robert A Weinberg, Jacqueline A Lees
Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called "tumor-initiating cells" (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment of the mammary epithelium, and their neoplastic counterparts, mammary TICs (MaTICs), are thought to serve as the TICs for the claudin-low subtype of breast cancer...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158255/nitro-fatty-acid-inhibition-of-triple-negative-breast-cancer-cell-viability-migration-invasion-and-tumor-growth
#8
Chen-Shan Chen Woodcock, Yi Huang, Steven R Woodcock, Sonia R Salvatore, Bhupinder Singh, Franca Golin-Bisello, Nancy E Davidson, Carola Neumann, Bruce A Freeman, Stacy G Wendell
Triple negative breast cancer (TNBC) comprises ~20% of all breast cancers and is the most aggressive mammary cancer subtype. Devoid of the estrogen and progesterone receptors, along with the receptor tyrosine kinase ERB2 (HER2) that define most mammary cancers, there are no targeted therapies for patients with TNBC. This, combined with a high metastatic rate and a lower 5-year survival rate than for other breast cancer phenotypes, means there is significant unmet need for new therapeutic strategies. Herein, the anti-neoplastic effects of the electrophilic fatty acid nitroalkene derivative, 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA), were investigated in multiple preclinical models of TNBC...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29156681/the-histone-demethylase-kdm3a-is-required-for-normal-epithelial-proliferation-ductal-elongation-and-tumor-growth-in-the-mouse-mammary-gland
#9
Li Qin, Yixiang Xu, Xiaobin Yu, Michael J Toneff, Dabing Li, Lan Liao, Jarrod D Martinez, Yi Li, Jianming Xu
Histone modification alters chromatin architecture to regulate gene transcription. KDM3A is a histone demethylase in the JmjC domain-containing protein family. It removes di- and mono- methyl residues from di- or mono-methylated lysine 9 of histone H3 (H3K9me2/me1). Recent studies have shown that Kdm3a plays an important role in self-renewal of embryonic stem cells, spermatogenesis, metabolism, sex determination and tumor angiogenesis. However, its role in mammary gland development and breast carcinogenesis remains unclear...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154377/tall-cell-variant-of-papillary-breast-carcinoma-an-additional-case-with-review-of-the-literature
#10
A Pitino, S Squillaci, C Spairani, P C Rassu, M F Cosimi
Papillary lesions of the breast can be one of the most challenging aspects of mammary pathology because of a wide morphologic spectrum that may be encountered in these lesions. An unusual breast tumor has been first classified as "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" and subsequently renamed "tall cell variant of papillary breast carcinoma". To our knowledge, only 13 cases of this neoplasm have been reported so far. Metastasis to the breast is not an uncommon event and about 5% of all such cases are of the thyroid origin...
September 2017: Pathologica
https://www.readbyqxmd.com/read/29154022/the-anti-tumor-effect-of-rankl-inhibition-in-malignant-solid-tumors-a-systematic-review
#11
REVIEW
A F de Groot, N M Appelman-Dijkstra, S H van der Burg, J R Kroep
At present, accumulating evidence suggests that inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) does not only induce an increase in bone mass and strength, but also has anti-tumor effects. Denosumab, an antibody targeting RANKL, is used to treat osteoporosis and to prevent skeletal related events (SREs) in patients with bone metastases originating from solid tumors. However, expression of RANKL and its receptor activator of nuclear factor kappa-B (RANK) is not solely restricted to cells involved in homeostasis of the bone and RANKL-RANK signalling appears to play a substantial role in many other processes in the body like mammary physiology, mammary tumorigenesis and the immune system...
November 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29152096/the-non-canonical-ubiquitin-activating-enzyme-uba6-suppresses-epithelial-mesenchymal-transition-of-mammary-epithelial-cells
#12
Xianpeng Liu, Limin Sun, Demirkan B Gursel, Chonghui Cheng, Sui Huang, Alfred W Rademaker, Seema A Khan, Jun Yin, Hiroaki Kiyokawa
Ubiquitination plays critical roles in the regulation of oncoproteins and tumor suppressors during carcinogenesis. The two ubiquitin activating enzymes (E1) in human genome, UBA1 and UBA6, initiate ubiquitination by ATP-dependent activation of ubiquitin. Recent evidence suggests that UBA1 and UBA6 play partially overlapped yet distinct roles in controlling the proteome. Here we demonstrate that ubiquitination pathways initiated specifically by UBA6 set a suppressive barrier against critical steps of mammary carcinogenesis such as loss of polarity, anoikis resistance and epithelial-mesenchymal transition (EMT)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151256/melatonin-and-metformin-diminish-oxidative-stress-in-heart-tissue-in-a-rat-model-of-high-fat-diet-and-mammary-carcinogenesis
#13
Natalia Kurhaluk, Bianka Bojkova, Marek Radkowski, Olga V Zaitseva, Svitlana Kyriienko, Urszula Demkow, Pawel J Winklewski
The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2...
November 19, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29151074/interferon-lambda-2-promotes-mammary-tumor-metastasis-via-angiogenesis-extension-and-stimulation-of-cancer-cell-migration
#14
R Pingwara, K Witt-Jurkowska, K Ulewicz, J Mucha, K Tonecka, Z Pilch, B Taciak, K Zabielska-Koczywas, M Mori, S Berardozzi, B Botta, T P Rygiel, M Krol
Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-λ2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-λ2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#15
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29142456/secretory-carcinoma-impact-of-translocation-and-gene-fusions-on-salivary-gland-tumor
#16
Ryoko Inaki, Masanobu Abe, Liang Zong, Takahiro Abe, Aya Shinozaki-Ushiku, Tetsuo Ushiku, Kazuto Hoshi
Secretory carcinoma (SC), previously described as mammary analogue secretory carcinoma (MASC), is a recently described salivary gland tumor which morphologically resembles mammary secretory carcinoma. The first description of SC/MASC, reported by Skálová et al. in 2010, was as a rare salivary carcinoma imitating secretory carcinoma of the breast. SC/MASC is a unique salivary gland tumor with morphological overlap with acinic cell carcinoma (AciCC), mucoepidermoid carcinoma (MEC), and adenocarcinoma not otherwise specified (ADC-NOS)...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#17
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29139009/lfm-a13-a-potent-inhibitor-of-polo-like-kinase-inhibits-breast-carcinogenesis-by-suppressing-proliferation-activity-and-inducing-apoptosis-in-breast-tumors-of-mice
#18
Kazim Sahin, Mehmet Tuzcu, Mehmet Yabas, Cemal Orhan, Nurhan Sahin, Ibrahim H Ozercan
The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage...
November 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29138800/broadleaf-mahonia-attenuates-granulomatous-lobular-mastitis%C3%A2-associated-inflammation-by-inhibiting-ccl%C3%A2-5-expression-in-macrophages
#19
Zhiyu Wang, Neng Wang, Xiaoyan Liu, Qi Wang, Biao Xu, Pengxi Liu, Huayu Zhu, Jianping Chen, Honglin Situ, Yi Lin
Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti‑inflammatory properties according to ancient records of traditional Chinese medicine...
November 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29137351/microrna-200-associated-with-metastatic-breast-cancer-promotes-traits-of-mammary-luminal-progenitor-cells
#20
Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii, Yibin Kang, Marian Martínez-Balbás, Stephen J Weiss, Jerónimo Blanco, Montserrat Muñoz, Pedro L Fernández, Timothy M Thomson
MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo...
October 13, 2017: Oncotarget
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