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Tumor growth factors in breast cancer

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https://www.readbyqxmd.com/read/28930982/development-of-a-human-preclinical-model-of-osteoclastogenesis-from-peripheral-blood-monocytes-co-cultured-with-breast-cancer-cell-lines
#1
Laura Mercatali, Chiara Spadazzi, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Federica Recine, Dino Amadori, Toni Ibrahim
The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We developed an in vitro fully human preclinical model of a co-culture of breast cancer cells and monocytes undergoing differentiation towards osteoclasts. We optimized a model of osteoclastogenesis starting from a sample of peripheral blood collected from healthy donors. Peripheral blood mononuclear cells (PBMCs) were first separated by density gradient centrifugation, seeded at a high density and induced to differentiate by adding two growth factors (GFs): receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF)...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28927692/prognostic-influence-of-tumor-stroma-on-breast-cancer-subtypes
#2
Sandra Cid, Noemi Eiro, Berta Fernández, Rosario Sánchez, Alejandro Andicoechea, Pablo Ignacio Fernández-Muñiz, Luis O González, Francisco J Vizoso
INTRODUCTION: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS: A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status)...
August 19, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#3
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925397/coactosin-like-protein-clp-cotl1-suppresses-breast-cancer-growth-through-activation-of-il-24-perp-and-inhibition-of-non-canonical-tgf%C3%AE-signaling
#4
L Xia, X Xiao, W L Liu, Y Song, T J J Liu, Y J Li, E Zacksenhaus, X J Hao, Y Ben-David
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28916978/tumor-biology-predicts-pathologic-complete-response-to-neoadjuvant-chemotherapy-in-patients-presenting-with-locally-advanced-breast-cancer
#5
Lori F Gentile, George Plitas, Emily C Zabor, Michelle Stempel, Monica Morrow, Andrea V Barrio
BACKGROUND: Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. OBJECTIVE: The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery...
September 15, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#6
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 12, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28915600/tumor-vasculogenic-mimicry-formation-as-an-unfavorable-prognostic-indicator-in-patients-with-breast-cancer
#7
Yanwei Shen, Jianfeng Quan, Mengying Wang, Shuting Li, Jiao Yang, Meng Lv, Zheling Chen, Lingxiao Zhang, Xiaoai Zhao, Jin Yang
Vasculogenic mimicry (VM), a newly defined pattern of tumor blood perfusion, describes the functional plasticity of aggressive tumor cells forming de novo vascular networks and is associated with the cancer progression and metastasis. However, the VM-positive rate and the impact of VM status on breast cancer patients' clinicopathological parameters and prognosis remain unclear. Thus, we performed a meta-analysis by incorporating all available evidence to clarify these issues. Eight studies that involved 1,238 breast cancer patients were eligible for inclusion in our study...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915583/n-acetylcysteine-breaks-resistance-to-trastuzumab-caused-by-muc4-overexpression-in-human-her2-positive-bc-bearing-nude-mice-monitored-by-89-zr-trastuzumab-and-18-f-fdg-pet-imaging
#8
Zéna Wimana, Geraldine Gebhart, Thomas Guiot, Bruno Vanderlinden, Denis Larsimont, Gilles Doumont, Gaetan Van Simaeys, Serge Goldman, Patrick Flamen, Ghanem Ghanem
Trastuzumab remains an important drug in the management of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer (BC). Several studies reported resistance mechanisms to trastuzumab, including impaired HER2-accessibility caused by mucin 4 (MUC4). Previously, we demonstrated an increase of Zirconium-89-radiolabeled-trastuzumab ((89)Zr-Trastuzumab) accumulation when MUC4-overexpressing BC-cells were challenged with the mucolytic drug N-Acetylcysteine (NAC). Hereby, using the same approach we investigated whether tumor exposure to NAC would also enhance trastuzumab-efficacy...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912898/inhibition-of-bone-marrow-derived-mesenchymal-stem-cells-homing-towards-triple-negative-breast-cancer-microenvironment-using-an-anti-pdgfr%C3%AE-aptamer
#9
Simona Camorani, Billy Samuel Hill, Raffaela Fontanella, Adelaide Greco, Matteo Gramanzini, Luigi Auletta, Sara Gargiulo, Sandra Albanese, Enrico Lucarelli, Laura Cerchia, Antonella Zannetti
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are shown to participate in tumor progression by establishing a favorable tumor microenvironment (TME) that promote metastasis through a cytokine networks. However, the mechanism of homing and recruitment of BM-MSCs into tumors and their potential role in malignant tissue progression is poorly understood and controversial. Here we show that BM-MSCs increase aggressiveness of triple-negative breast cancer (TNBC) cell lines evaluated as capability to migrate, invade and acquire stemness markers...
2017: Theranostics
https://www.readbyqxmd.com/read/28912144/androgen-and-estrogen-receptor-imaging-in-metastatic-breast-cancer-patients-as-a-surrogate-for-tissue-biopsies
#10
Clasina M Venema, Lemonitsa H Mammatas, Carolina P Schröder, Michel van Kruchten, Giulia Apollonio, Andor W J M Glaudemans, A H H Bongaerts, Otto S Hoekstra, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F de Vries, Elisabeth G E de Vries, Ronald Boellaard, Catharina Willemien Menke-van der Houven van Oordt, Geke Ap Hospers
In addition to the well-known estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by (18)F-fluoroestradiol (FES) PET, and AR expression has been visualized in prostate cancer patients with (18)F-fluorodihydrotestosterone (FDHT) PET. Our aim was to assess the concordance between FDHT- and FES-PET and tumor AR- and ER-expression measured immunohistochemically (IHC) in patients with metastatic breast cancer...
September 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28911087/an-antisense-oligonucleotide-targeting-tgf-%C3%AE-2-inhibits-lung-metastasis-and-induces-cd86-expression-in-tumor-associated-macrophages
#11
I Huber-Ruano, C Raventós, I Cuartas, C Sánchez-Jaro, A Arias, J L Parra, K Wosikowski, M Janicot, J Seoane
Background: The transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28911002/intratumor-heterogeneity-predicts-metastasis-of-triple-negative-breast-cancer
#12
Fang Yang, Yucai Wang, Quan Li, Lulu Cao, Zijia Sun, Juan Jin, Hehui Fang, Aiyu Zhu, Yan Li, Wenwen Zhang, Yanru Wang, Hui Xie, Jan-Åke Gustafsson, Shui Wang, Xiaoxiang Guan
Even with the identical clinicopathological features, the ability for metastasis is vastly different among triple-negative breast cancer (TNBC) patients. Intratumor heterogeneity (ITH), which is common in breast cancer, may be a key mechanism leading to the tumor progression. In this study, we studied whether a quantitative genetic definition of ITH can predict clinical outcomes in patients with TNBC. We quantified ITH by calculating Shannon index, a measure of diversity in a population, based on Myc, epidermal growth factor receptor/centromeric probe 7 (EGFR/CEP7) and cyclin D1/centromeric probe 11 (CCND1/CEP11) copy number variations (CNVs) in 300 cells at three different locations of a tumor...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28903441/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#13
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive. We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903409/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#14
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903399/phosphatidylcholine-specific-phospholipase-c-inhibition-reduces-her2-overexpression-cell-proliferation-and-in-vivo-tumor-growth-in-a-highly-tumorigenic-ovarian-cancer-model
#15
Luisa Paris, Franca Podo, Francesca Spadaro, Laura Abalsamo, Maria Elena Pisanu, Alessandro Ricci, Serena Cecchetti, Luisa Altabella, Maria Buoncervello, Ludmila Lozneanu, Marina Bagnoli, Carlo Ramoni, Silvana Canevari, Delia Mezzanzanica, Egidio Iorio, Rossella Canese
Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903348/nuclear-receptor-nr4a1-is-a-tumor-suppressor-down-regulated-in-triple-negative-breast-cancer
#16
Hongmei Wu, Jiong Bi, Yan Peng, Lei Huo, Xiaobin Yu, Zhihui Yang, Yunyun Zhou, Li Qin, Yixiang Xu, Lan Liao, Yang Xie, Orla M Conneely, Jos Jonkers, Jianming Xu
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902197/fast-and-reproducible-isers-microscopy-of-single-her2-positive-breast-cancer-cells-using-gold-nanostars-as-sers-nanotags
#17
Xin-Ping Wang, Bernd Walkenfort, Matthias König, Lisa König, Sabine Kasimir-Bauer, Sebastian Schlücker
Speed is often a bottleneck in conventional Raman microscopy on biological specimens. In immuno-Raman microspectroscopy, or for short iSERS microscopy, the acquisition times per pixel have been reduced by more than one order of magnitude over the past decade since its proof of concept. Typically rather high laser power densities are employed with the intention of compensating for the shorter acquisition times, without checking the reproducibility of the results in repeated experiments on the same sample. Here, we systematically analyze this aspect at the single-cell level since it forms the basis of quantification and is very important for reinspection of the same specimen...
September 13, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/28901268/nrg1-erbb-lost-in-translation-a-new-paradigm-for-lung-cancer
#18
Domenico Trombetta, Antonio Rossi, Federico Pio Fabrizio, A Sparaneo, Paolo Graziano, Vito Michele Fazio, Lucia Anna Muscarella
The ErbB network of receptor tyrosine kinases represents one of the best examples of how the understanding of molecular basis of tumor pathogenesis can give a significant improvement for patients treatment, suggesting new therapeutic options to overcome acquired treatment resistance. This amazing bridge between growth factor receptors and cancer has been consolidated during the last decades through the identification of many driver mutations in the gene key of the RTKs network. Unexpected molecular lesions of the NRG1 gene followed by an aberrant ErbB signaling were recently described as a new molecular features of non-small cell lung cancer, but it has been also sporadically reported in other tumors...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28900173/fgfr-inhibitor-azd4547-impedes-the-stemness-of-mammary-epithelial-cells-in-the-premalignant-tissues-of-mmtv-erbb2-transgenic-mice
#19
Qingxia Zhao, Amanda B Parris, Erin W Howard, Ming Zhao, Zhikun Ma, Zhiying Guo, Ying Xing, Xiaohe Yang
The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases (RTKs) regulates signaling pathways involved in cell proliferation and differentiation. Currently, the anti-tumor properties of FGFR inhibitors are being tested in preclinical and clinical studies. Nevertheless, reports on FGFR inhibitor-mediated breast cancer prevention are sparse. In this study, we investigated the anti-cancer benefits of AZD4547, an FGFR1-3 inhibitor, in ErbB2-overexpressing breast cancer models. AZD4547 (1-5 µM) demonstrated potent anti-proliferative effects, inhibition of stemness, and suppression of FGFR/RTK signaling in ErbB2-overexpressing human breast cancer cells...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899409/alcohol-consumption-and-breast-tumor-gene-expression
#20
Jun Wang, Yujing J Heng, A Heather Eliassen, Rulla M Tamimi, Aditi Hazra, Vincent J Carey, Christine B Ambrosone, Victor P de Andrade, Adam Brufsky, Fergus J Couch, Tari A King, Francesmary Modugno, Celine M Vachon, David J Hunter, Andrew H Beck, Susan E Hankinson
BACKGROUND: Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood. METHODS: We analyzed messenger RNA (mRNA) microarray data from both invasive breast tumors (N = 602) and tumor-adjacent normal tissues (N = 508) from participants diagnosed with breast cancer in the Nurses' Health Study (NHS) and NHSII...
September 12, 2017: Breast Cancer Research: BCR
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