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"Targeted therapy" AND breast

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https://www.readbyqxmd.com/read/28427809/picrasidine-g-decreases-viability-of-mda-mb-468-egfr-overexpressing-triple-negative-breast-cancer-cells-through-inhibition-of-egfr-stat3-signaling-pathway
#1
Naoya Yamashita, Manami Kondo, Shuai Zhao, Wei Li, Kazuo Koike, Kiyomitsu Nemoto, Yuichiro Kanno
Targeted therapy is unavailable for treating patients with triple-negative breast cancer (TNBC), which accounts for approximately 15% of all breast cancers. Overexpression of epidermal growth factor receptor (EGFR) is observed in approximately 30-60% of TNBCs. Therefore, developing novel strategies for inhibiting EGFR signaling is required. In the present study, a natural compound library was screened to identify molecules that target TNBCs that overexpress EGFR. Picrasidine G (PG), a naturally occurring dimeric alkaloid produced by Picrasma quassioides, decreased the viability of the MDA-MB 468 cell line (TNBC(EGFR+)) compared with other breast cancer cell lines...
March 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28425453/aptamer-mediated-impairment-of-egfr-integrin-%C3%AE-v%C3%AE-3-complex-inhibits-vasculogenic-mimicry-and-growth-of-triple-negative-breast-cancers
#2
Simona Camorani, Elvira Crescenzi, Matteo Gramanzini, Monica Fedele, Antonella Zannetti, Laura Cerchia
Current treatment options for triple-negative breast cancers (TNBCs) is limited by the absence of well-defined biomarkers, excluding a targeted therapy. Notably, epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of TNBCs and is a negative prognostic factor. In clinical trials, however, existing EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a valid alternative to antibodies for diagnostic and therapeutic uses. Here, we prove that, when applied to aggressive TNBC cell lines with unique stem-like plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents the vasculogenic mimicry (VM) capability of the cells and destroys previously formed channels in three-dimensional culture...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423528/level-of-fact-defines-the-transcriptional-landscape-and-aggressive-phenotype-of-breast-cancer-cells
#3
Daria Fleyshman, Laura Prendergast, Alfiya Safina, Geraldine Paszkiewicz, Mairead Commane, Kelsey Morgan, Kristopher Attwood, Katerina Gurova
Although breast cancer (BrCa) may be detected at an early stage, there is a shortage of markers that predict tumor aggressiveness and a lack of targeted therapies. Histone chaperone FACT, expressed in a limited number of normal cells, is overexpressed in different types of cancer, including BrCa. Recently, we found that FACT expression in BrCa correlates with markers of aggressive BrCa, which prompted us to explore the consequences of FACT inhibition in BrCa cells with varying levels of FACT.FACT inhibition using a small molecule or shRNA caused reduced growth and viability of all BrCa cells tested...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422142/g-protein-coupled-kiss1-receptor-is-overexpressed-in-triple-negative-breast-cancer-and-promotes-drug-resistance
#4
Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya
Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420393/medical-treatment-of-mammary-desmoid-type-fibromatosis-which-benefit
#5
Louise Scheer, Massimo Lodi, Sébastien Molière, Jean-Emmanuel Kurtz, Carole Mathelin
BACKGROUND: Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action...
April 18, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28415567/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#6
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414093/imbalance-in-leptin-adiponectin-levels-and-leptin-receptor-expression-as-chief-contributors-to-triple-negative-breast-cancer-progression-in-northeast-india
#7
Rizwana Sultana, Amal Ch Kataki, Bibhuti Bhusan Borthakur, Tarun K Basumatary, Sujoy Bose
BACKGROUND: Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented...
April 14, 2017: Gene
https://www.readbyqxmd.com/read/28412736/tumor-biology-clinicopathological-characteristics-and-prognosis-of-screen-detected-t1-invasive-non-palpable-breast-cancer-in-asymptomatic-chinese-women-2001-2014
#8
Bo Pan, Ru Yao, Yi-Dong Zhou, Qing-Li Zhu, Jie Shi, Qian-Qian Xu, Chang-Jun Wang, Shan-Shan You, Feng Mao, Yan Lin, Song-Jie Shen, Zhi-Yong Liang, Yu-Xin Jiang, Qiang Sun
BACKGROUND: Mammography screening usually detects low-risk breast cancer in the western world. However, little is known about the ultrasound and mammography screen-detected T1 invasive non-palpable breast cancer (NPBC) in asymptomatic Chinese women. RESULTS: With the increase of tumor size (T1a, b, c), lymph node positivity (8.7%, 18.3%, 26.0%, p = 0.018), pN (p = 0.028) and TNM stage (p = 0.035) increased accordingly. Tumor size (T1a, b, c) was correlated with high Ki-67 index (defined as ≥ 14%, 37...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412238/chitosan-modified-plga-nanoparticles-tagged-with-5tr1-aptamer-for-in-vivo-tumor-targeted-drug-delivery
#9
Sahar Taghavi, Mohammad Ramezani, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi
In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) modified with chitosan (CS) through a physical adsorption method. Using chitosan, the solubility and surface charge of PLGA was modified to make efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against the MUC1 receptor. To prove the MUC1 receptor-mediated uptake of Epi-PLGA-CS-Apt NPs in the cells, competition experiments were carried out...
April 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28410844/folate-receptor-alpha-expression-is-associated-with-increased-risk-of-recurrence-in-triple-negative-breast-cancer
#10
Paula S Ginter, Patrick J McIntire, Xiaoyan Cui, Lina Irshaid, Yifang Liu, Zhengming Chen, Sandra J Shin
BACKGROUND: Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein expression is enriched in triple-negative breast cancer (TNBC) and associated with poor prognosis in all breast cancer types. Newly developed anti-FOLR1 therapy could potentially be used in patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value...
March 21, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28405494/overcoming-resistance-to-her2-targeted-therapy-with-a-novel-her2-cd3-bispecific-antibody
#11
Andres Lopez-Albaitero, Hong Xu, Hongfen Guo, Linlin Wang, Zhihao Wu, Hoa Tran, Sarat Chandarlapaty, Maurizio Scaltriti, Yelena Janjigian, Elisa de Stanchina, Nai-Kong V Cheung
T-cell-based therapies have emerged as one of the most clinically effective ways to target solid and non-solid tumors. HER2 is responsible for the oncogenesis and treatment resistance of several human solid tumors. As a member of the HER family of tyrosine kinase receptors, its over-activity confers unfavorable clinical outcome. Targeted therapies directed at this receptor have achieved responses, although development of resistance is common. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform that while preserving the anti-proliferative effects of trastuzumab, it recruits and activates non-specific circulating T-cells, promoting T cell tumor infiltration and ablating HER2(+) tumors, even when these are resistant to standard HER2-targeted therapies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404630/mir-424-322-503-is-a-breast-cancer-tumor-suppressor-whose-loss-promotes-resistance-to-chemotherapy
#12
Ruth Rodriguez-Barrueco, Erin A Nekritz, François Bertucci, Jiyang Yu, Felix Sanchez-Garcia, Tizita Z Zeleke, Andrej Gorbatenko, Daniel Birnbaum, Elena Ezhkova, Carlos Cordon-Cardo, Pascal Finetti, David Llobet-Navas, Jose M Silva
The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28400538/the-transcription-factor-mafk-induces-emt-and-malignant-progression-of-triple-negative-breast-cancer-cells-through-its-target-gpnmb
#13
Yukari Okita, Minori Kimura, Rudy Xie, Chen Chen, Larina Tzu-Wei Shen, Yurika Kojima, Hiroyuki Suzuki, Masafumi Muratani, Masao Saitoh, Kentaro Semba, Carl-Henrik Heldin, Mitsuyasu Kato
Triple-negative breast cancer (TNBC) is particularly aggressive and difficult to treat. For example, the transforming growth factor-β (TGF-β) pathway is implicated in TNBC progression and metastasis, but its opposing role in tumor suppression in healthy tissues and early-stage lesions makes it a challenging target. Therefore, additional molecular characterization of TNBC may lead to improved patient prognosis by informing the development and optimum use of targeted therapies. We found that musculoaponeurotic fibrosarcoma (MAF) oncogene family protein K (MAFK), a member of the small MAF family of transcription factors that are induced by the TGF-β pathway, was abundant in human TNBC and aggressive mouse mammary tumor cell lines...
April 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28396358/extracellular-matrix-integrin-signaling-promotes-resistance-to-combined-inhibition-of-her2-and-pi3k-in-her2-breast-cancer
#14
Ariella B Hanker, Monica Valeria Estrada, Giampaolo Bianchini, Preston D Moore, Junfei Zhao, Feixiong Cheng, Luca Gianni, James P Koch, Darren R Tyson, Violeta Sanchez, Brent N Rexer, Melinda Sanders, Zhongming Zhao, Thomas Stricker, Carlos L Arteaga
PIK3CA mutations are associated with resistance to HER2-targeted therapies. We previously showed that HER2+/PIK3CA(H1047R) transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K. TPB-resistant tumors were generated by treating HER2+/PIK3CA(H1047R) mice long-term with the drug combination. RNA-sequencing of TPB-resistant tumors revealed that extracellular matrix (ECM) and cell adhesion genes, including collagen II (Col2a1), were markedly upregulated, accompanied by activation of integrin β1/Src...
April 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28394344/aberrant-low-expression-of-p85%C3%AE-in-stromal-fibroblasts-promotes-breast-cancer-cell-metastasis-through-exosome-mediated-paracrine-wnt10b
#15
Y Chen, C Zeng, Y Zhan, H Wang, X Jiang, W Li
P85α, which acts as a tumour suppressor, is frequently found to be downregulated in various human cancers. However, the role of p85α in the tumour microenvironment is unknown. Here, we report that aberrantly low expression of p85α in breast cancer stroma is clinically relevant to breast cancer disease progression. Stromal fibroblasts can acquire the hallmarks of cancer-associated fibroblasts (CAFs) as a result of the loss of p85α expression. Paracrine Wnt10b from p85α-deficient fibroblasts can promote cancer progression via epithelial-to-mesenchymal transition (EMT) induced by the canonical Wnt pathway...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28393242/overexpression-of-srcin1-contributes-to-the-growth-and-metastasis-of-colorectal-cancer
#16
Mengnan Zhang, Feng Ma, Ruyi Xie, Yao Wu, Meiyan Wu, Pei Zhang, Ying Peng, Jinjun Zhao, Jing Xiong, Aimin Li, Cheng Kequan, Yali Zhang, Side Liu, Jide Wang, Xueqing Chen
The adaptor protein Srcin1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Srcin1 behaves as a tumour suppressor in breast cancer, but the role of Srcin1 in the development of colorectal cancer (CRC) remains unknown. In the present study, Srcin1 expression in normal tissue was examined by tissue microarray and assessed by immunohistochemistry in 10 patients. In addition, the biological impact of Srcin1 knockdown on CRC cells was investigated in vitro and in vivo...
April 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28392805/cadherins-associate-with-distinct-stem-cell-related-transcription-factors-to-coordinate-the-maintenance-of-stemness-in-triple-negative-breast-cancer
#17
Chuanwei Yang, Xuemei Zhao, Naipeng Cui, Yulong Liang
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28391295/diagnosis-and-treatment-of-brain-metastases-from-solid-tumors-guidelines-from-the-european-association-of-neuro-oncology-eano
#18
Riccardo Soffietti, Ufuk Abacioglu, Brigitta Baumert, Stephanie E Combs, Sara Kinhult, Johan M Kros, Christine Marosi, Philippe Metellus, Alexander Radbruch, Salvador S Villa Freixa, Michael Brada, Carmine M Carapella, Matthias Preusser, Emilie Le Rhun, Roberta Rudà, Joerg C Tonn, Damien C Weber, Michael Weller
The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options...
February 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28387221/a-3q-gene-signature-associated-with-triple-negative-breast-cancer-organ-specific-metastasis-and-response-to-neoadjuvant-chemotherapy
#19
Jun Qian, Heidi Chen, Xiangming Ji, Rosana Eisenberg, A Bapsi Chakravarthy, Ingrid A Mayer, Pierre P Massion
Triple negative breast cancers (TNBC) are aggressive tumors, with high rates of metastatic spread and targeted therapies are critically needed. We aimed to assess the prognostic and predictive value of a 3q 19-gene signature identified previously from lung cancer in a collection of 4,801 breast tumor gene expression data. The 3q gene signature had a strong association with features of aggressiveness such as high grade, hormone receptor negativity, presence of a basal-like or TNBC phenotype and reduced distant metastasis free survival...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386369/prognostic-role-of-lymphatic-vessel-density-and-lymphovascular-invasion-in-chemotherapy-naive-and-chemotherapy-treated-patients-with-invasive-breast-cancer
#20
Joanna A Niemiec, Agnieszka Adamczyk, Aleksandra Ambicka, Anna Mucha-Małecka, Wojciech M Wysocki, Beata Biesaga, Marek Ziobro, Ida Cedrych, Aleksandra Grela-Wojewoda, Małgorzata Domagała-Haduch, Joanna Wysocka, Janusz Ryś, Beata Sas-Korczyńska
It is assumed that the spread of breast cancer cells via the lymphatic system might be influenced by inflammatory reactions and/or the application of chemotherapy or molecularly targeted therapy. Therefore, we analysed survival according to lymphatic vessel density (LVD), lymphovascular invasion (LVI) (both assessed using podoplanin as immunohistochemical marker of lymphatic endothelium) and well-established clinico-pathological features in a group of 358 patients with invasive ductal breast cancer: 139 chemotherapy-naïve (pT1-2/pN0/M0) and 219 treated with chemotherapy (pT1-4/pN1-3/M0)...
2017: American Journal of Translational Research
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