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https://www.readbyqxmd.com/read/28813674/an-integrated-systems-biology-approach-identifies-trim25-as-a-key-determinant-of-breast-cancer-metastasis
#1
Logan A Walsh, Mariano J Alvarez, Erich Y Sabio, Marsha Reyngold, Vladimir Makarov, Suranjit Mukherjee, Ken-Wing Lee, Alexis Desrichard, Şevin Turcan, Martin G Dalin, Vinagolu K Rajasekhar, Shuibing Chen, Linda T Vahdat, Andrea Califano, Timothy A Chan
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#2
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28810596/expression-of-kruppel-like-factor-8-and-ki67-in-lung-adenocarcinoma-and-prognosis
#3
Yifei Liu, Xiufang Yao, Qing Zhang, Li Qian, Jia Feng, Tingting Bian, Jianguo Zhang, Ye Tian
Kruppel-like factor 8 (KLF8) belongs to the KLF family and has various roles in the regulation of the cell cycle, proliferation and tumor genesis. KLF8 is overexpressed in gastric, ovarian, breast and renal cancer. Additionally, KLF8 may affect invasion and metastasis of tumors. However, whether KLF8 also acts as an ontogeny in lung adenocarcinoma (LAC) remains unknown. The aim of the present study was to determine the association between KLF8 expression and various clinical and pathological parameters. Western blot assays and immune histochemistry analyses revealed that KLF8 level in LAC tissues was higher than that in the normal lung tissues and KLF8 expression was significantly associated with clinical variables (P<0...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810579/microrna-375-targets-pax6-and-inhibits-the-viability-migration-and-invasion-of-human-breast-cancer-mcf-7-cells
#4
Qiongyan Zou, Wenjun Yi, Jianghai Huang, Fenfen Fu, Gannong Chen, Dewu Zhong
MicroRNAs (miRs) are a type of small non-coding RNA that serve crucial roles in the development and progression of breast cancer. However, the exact role and underlying molecular mechanism of miR-375 in mediating the growth and metastasis of breast cancer remains unknown. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to examine RNA and protein expression. A luciferase reporter assay was performed to determine the association between miR-375 and paired box 6 (PAX6)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810186/the-efficacy-of-lapatinib-and-capecitabine-in-her-2-positive-breast-cancer-with-brain-metastases-a-systematic-review-and-pooled-analysis
#5
REVIEW
Fausto Petrelli, Michele Ghidini, Veronica Lonati, Gianluca Tomasello, Karen Borgonovo, Mara Ghilardi, Mary Cabiddu, Sandro Barni
INTRODUCTION: Breast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs. MATERIAL AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials...
August 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28810140/new-views-into-the-genetic-landscape-of-metastatic-breast-cancer
#6
Xiaoyu Zhao, Scott Powers
Whether metastasis-specific genetic alterations exist remains controversial. The study by Yates et al. in this issue of Cancer Cell provides evidence that metastases emerge late during primary breast cancer progression and that additional driver mutations are often acquired, posing both challenges and opportunities for precision treatment of metastatic breast cancer.
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28808873/elevated-hu-antigen-receptor-hur-expression-is-associated-with-tumor-aggressiveness-and-poor-prognosis-but-not-with-cox-2-expression-in-invasive-breast-carcinoma-patients
#7
Constantinos Giaginis, Anastasia Sampani, Iolly Kotta-Loizou, Ioanna Giannopoulou, Eugene Danas, Ekaterini Politi, Gerasimos Tsourouflis, Gregorios Kouraklis, Efstratios Patsouris, Antonios Keramopoulos, Lydia Nakopoulou, Stamatios Theocharis
Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival...
August 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28808484/er%C3%AE-and-er%C3%AE-co-expression-an-indicator-of-aggressive-tumors-and-hormonal-sensitivity
#8
Mohamed Oueslati, Ilhem Bittaieb, Nadia Sassi, Awatef Ben Jemaa, Amor Gamoudi, Khaled Rahal, Ridha Oueslati
The estrogen receptors (ERs) ERα and ERβ are important factors in breast cancer progression. Nevertheless, the molecular interplay between ERα and ERβ and its clinical significance in breast cancer is controversial. The establishment of a clear association is required; therefore, the current study analyzed the expression patterns of ERα and ERβ in 32 breast tumor tissues using reverse transcription-quantitative polymerase chain reaction. Furthermore, human epidermal growth factor receptor 2 (HER2) and the Ki-67 status were detected by immunohistochemistry...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808311/antitumor-properties-of-coenzyme-q0-against-human-ovarian-carcinoma-cells-via-induction-of-ros-mediated-apoptosis-and-cytoprotective-autophagy
#9
You-Cheng Hseu, Tai-Jung Tsai, Mallikarjuna Korivi, Jer-Yuh Liu, Hui-Jye Chen, Chung-Ming Lin, Yi-Chun Shen, Hsin-Ling Yang
Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808208/effects-of-bisphenol-compounds-on-the-growth-and-epithelial-mesenchymal-transition-of-mcf-7-cv-human-breast-cancer-cells
#10
Ji-Youn Kim, Ho-Gyu Choi, Hae-Miru Lee, Geum-A Lee, Kyung-A Hwang, Kyung-Chul Choi
Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical (EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-dependent cancer has been reported rarely compared with the numerous cases of BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors (ERs)...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28808045/fighting-tubulin-targeting-anticancer-drug-toxicity-and-resistance
#11
REVIEW
Roberta Visconti, Domenico Grieco
Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28807940/mitotic-vulnerability-in-triple-negative-breast-cancer-associated-with-lin9-is-targetable-with-bet-inhibitors
#12
Jennifer M Sahni, Sylvia S Gayle, Bryan Webb, Kristen L Weber-Bonk, Darcie D Seachrist, Salendra Singh, Steven T Sizemore, Nicole A Restrepo, Gurkan Bebek, Peter Scacheri, Vinay Varadan, Matthew K Summers, Ruth A Keri
Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of Bromodomain and extraterminal protein inhibitors (BETi) in TNBC revealed these drugs cause multinucleation, indicating BET proteins are essential for efficient mitosis and cytokinesis. Here, using live cell imaging, we show that BET inhibition prolonged mitotic progression and induced mitotic cell death, both of which are indicative of mitotic catastrophe...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807821/popdc1-is-suppressed-in-human-breast-cancer-tissues-and-is-negatively-regulated-by-egfr-in-breast-cancer-cell-lines
#13
Johanna Ndamwena Amunjela, Steven John Tucker
Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status...
August 11, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28805661/the-foxn3-neat1-sin3a-repressor-complex-promotes-progression-of-hormonally-responsive-breast-cancer
#14
Wanjin Li, Zihan Zhang, Xinhua Liu, Xiao Cheng, Yi Zhang, Xiao Han, Yu Zhang, Shumeng Liu, Jianguo Yang, Bosen Xu, Lin He, Luyang Sun, Jing Liang, Yongfeng Shang
The pathophysiological function of the forkhead transcription factor FOXN3 remains to be explored. Here we report that FOXN3 is a transcriptional repressor that is physically associated with the SIN3A repressor complex in estrogen receptor-positive (ER+) cells. RNA immunoprecipitation-coupled high-throughput sequencing identified that NEAT1, an estrogen-inducible long noncoding RNA, is required for FOXN3 interactions with the SIN3A complex. ChIP-Seq and deep sequencing of RNA genomic targets revealed that the FOXN3-NEAT1-SIN3A complex represses genes including GATA3 that are critically involved in epithelial-to-mesenchymal transition (EMT)...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28802099/cancer-associated-fibroblasts-autophagy-enhances-progression-of-triple-negative-breast-cancer-cells
#15
Mengchuan Wang, Jian Zhang, Yizhe Huang, Shufeng Ji, Guoli Shao, Shaobo Feng, Danxun Chen, Kankan Zhao, Zixiang Wang, Aiguo Wu
BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts...
August 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28802057/hmgb1-released-by-autophagic-cancer-associated-fibroblasts-maintains-the-stemness-of-luminal-breast-cancer-cells
#16
Xi-Long Zhao, Yong Lin, Jun Jiang, Zhuo Tang, Shuai Yang, Lu Lu, Yan Liang, Xue Liu, Jiao Tan, Xu-Gang Hu, Qin Niu, Wen-Juan Fu, Ze-Xuan Yan, De-Yu Guo, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Hsiang-Fu Kung, Xiu-Wu Bian, Xiao-Hong Yao
Cancer stem/initiating cells (CSCs/CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer associated fibroblasts (CAFs) are major components of the niche of breast cancer initiating cells (BCICs) and their interactions may profoundly affect breast cancer progression. Autophagy has been considered as a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance remains elusive...
August 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28801789/multimodal-laser-ablation-desorption-imaging-analysis-of-zn-and-mmp-11-in-breast-tissues
#17
Raquel González de Vega, María Luisa Fernández Sanchez, Noemí Eiro, Francisco J Vizoso, Michael Sperling, Uwe Karst, Alfredo Sanz Medel
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. The main functions of these metalloproteinases are the degradation of the stromal connective tissue and basement membrane components. Recent data from model systems suggest that MMPs are involved in breast cancer (BC) initiation, invasion, and metastasis. Particularly, MMP-11 (stromelysin-3) is expressed in stromal fibroblasts adjacent to epithelial tumor cells, and high levels of this metalloproteinase were associated with tumor progression and poor prognosis of BC...
August 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28801478/phosphatases-and-solid-tumors-focus-on-glioblastoma-initiation-progression-and-recurrences
#18
REVIEW
Matthias Dedobbeleer, Estelle Willems, Stephen Freeman, Arnaud Lombard, Nicolas Goffart, Bernard Rogister
Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma...
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28801472/breast-cancer-immunotherapy-facts-and-hopes
#19
Leisha A Emens
Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of PD-1/PD-L1 antagonists in small numbers of metastatic breast cancer patients. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of TILs. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple negative breast cancer (TNBC), suggesting these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert non-responders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy...
August 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28800861/ipatasertib-plus-paclitaxel-versus-placebo-plus-paclitaxel-as-first-line-therapy-for-metastatic-triple-negative-breast-cancer-lotus-a-multicentre-randomised-double-blind-placebo-controlled-phase-2-trial
#20
Sung-Bae Kim, Rebecca Dent, Seock-Ah Im, Marc Espié, Sibel Blau, Antoinette R Tan, Steven J Isakoff, Mafalda Oliveira, Cristina Saura, Matthew J Wongchenko, Amy V Kapp, Wai Y Chan, Stina M Singel, Daniel J Maslyar, José Baselga
BACKGROUND: The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer. The LOTUS trial investigated the addition of ipatasertib to paclitaxel as first-line therapy for triple-negative breast cancer. METHODS: In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium...
August 8, 2017: Lancet Oncology
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