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Targeted therapy in breast cancer

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https://www.readbyqxmd.com/read/28108861/in-vivo-magnetic-resonance-imaging-investigating-the-development-of-experimental-brain-metastases-due-to-triple-negative-breast-cancer
#1
Amanda M Hamilton, Paula J Foster
Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge...
January 21, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28108739/targeting-oncogenic-vulnerabilities-in-triple-negative-breast-cancer-biological-bases-and-ongoing-clinical-studies
#2
Alberto Ocana, Atanasio Pandiella
Triple negative breast cancer (TNBC) is still an incurable disease despite the great scientific effort performed during the last years. The huge heterogeneity of this disease has motivated the evaluation of a great number of therapies against different molecular alterations. In this article, we review the biological bases of this entity and how the known molecular evidence supports the current preclinical and clinical development of new therapies. Special attention will be given to ongoing clinical studies and potential options for future drug combinations...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108732/fak-regulates-e-cadherin-expression-via-p-srcy416-p-erk1-2-p-stat3y705-and-ppar%C3%AE-mir-125b-stat3-signaling-pathway-in-b16f10-melanoma-cells
#3
Guoshun Pei, Yan Lan, Dianhua Chen, Lina Ji, Zi-Chun Hua
Focal adhesion kinase (FAK) is involved in tumor cell migration and metastasis. However, the underlying mechanism remains unclear. Here, we present a signaling pathway involved in the regulation of melanoma cell migration by FAK. We found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. The down-regulation of FAK inhibited the expression of p-SrcY416, p-ERK1/2, Stat3 and p-Stat3Y705, while promoted the expression of PPARγ, miR-125b and E-cadherin...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#4
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
: Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
November 15, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108622/a-genome-wide-loss-of-function-screen-identifies-slc26a2-as-a-novel-mediator-of-trail-resistance
#5
Lina Dimberg, Christina G Towers, Kian Behbakht, Taylor Hotz, Jihye Kim, Susan P Fosmire, Christopher C Porter, Aik-Choon Tan, Andrew Thorburn, Heide L Ford
: TNF-related apoptosis inducing ligand (TRAIL) is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108260/triple-negative-metastatic-breast-cancer-is-dependent-on-sphks-s1p-signaling-for-growth-and-survival
#6
Aparna Maiti, Kazuaki Takabe, Nitai C Hait
About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#7
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28107508/prospects-of-targeting-the-gastrin-releasing-peptide-receptor-and-somatostatin-receptor-2-for-nuclear-imaging-and-therapy-in-metastatic-breast-cancer
#8
Simone U Dalm, Willemijne A M E Schrijver, Anieta M Sieuwerts, Maxime P Look, Angelique C J Ziel-van der Made, Vanja de Weerd, John W Martens, Paul J van Diest, Marion de Jong, Carolien H M van Deurzen
BACKGROUND: The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC. METHODS: mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction...
2017: PloS One
https://www.readbyqxmd.com/read/28106614/study-of-intrapatient-variability-and-reproducibility-of-quantitative-tumor-perfusion-parameters-evaluated-with-dynamic-contrast-enhanced-ultrasonography
#9
Nathalie Lassau, Bénédicte Coiffier, Laura Faivre, Baya Benatsou, Sophie Bidault, Elizabeth Girard, Bernard Asselain, Stéphanie Pitre-Champagnat, Serge Koscielny
OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation...
January 18, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28106540/detection-of-human-breast-cancer-cells-using-a-2-deoxy-d-glucose-functionalized-superparamagnetic-iron-oxide-nanoparticles
#10
Xiu-Hong Shan, Peng Wang, Fei Xiong, Hao-Yue Lu, Hui Hu
BACKGROUND: Breast cancer is one of the most common type of female cancer worldwide and represents 14% of cancer-related deaths in women. Early detection is the most important factor for treatment and prognosis of breast cancer. In most countries, the women are currently screened with mammography only. Even though there has been considerable progress in the detection, surgical therapy, hormonal and target therapy of breast cancer, there are about ∼ 3500 000 women who die from breast cancer each year...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106372/folate-engineered-microvesicles-for-enhanced-target-and-synergistic-therapy-towards-breast-cancer
#11
Lian Zhu, Di Dong, Zi-Li Yu, Yi-Fang Zhao, Dai-Wen Pang, Zhi-Ling Zhang
As an ideal nanovector candidate, microvesicles (MVs) have been gradually utilized for packaging kinds of functional molecules for effective tumor diagnosis and therapy; however, the deficiency of their tumor targeting influenced their therapy efficacy. Through a facile phospholipid substitution strategy, MVs based drug delivery system (DDS) was apparently endowed with high tumor targeting towards breast cancer thanks to the modified folate onto the membrane of MVs, simultaneously possessed of synergistic anti-tumor effect, and in vivo tumor imaging attributed to the SA-QDs labeling...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28105180/screening-specific-polypeptides-of-breast-cancer-stem-cells-from-a-phage-display-random-peptide-library
#12
Fei Liu, Chun-Ling Qi, Mian Kong, Ting-Ting Liu, Lei Li, Bao-Jiang Li
The present study aimed to identify polypeptides that specifically bond to breast cancer stem cells from a phage display random 12 peptide library, in addition to the affinity and specificity of polypeptides. A phage display random 12 peptide library was screened using breast cancer stem cells as targets isolated from the MDA-MB-231 cell line using the serum-free culture technique with hs578bst and MDA-MB-231 cells as subtract-screening cells. Positive and specific binding clones were amplified and sent for sequencing...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104744/spect-ct-imaging-of-the-novel-her2-targeted-peptide-probe-99mtc-hynic-h6f-in-breast-cancer-mouse-models
#13
Liqiang Li, Yue Wu, Zihua Wang, Bing Jia, Zhiyuan Hu, Chengyan Dong, Fan Wang
OBJECTIVES: Overexpression of human epidermal growth factor receptor 2 (HER2) plays important roles in tumorigenesis and tumor progression in breast cancer. Nuclear imaging of HER2 expression in tumors might detect all HER2-positive tumors throughout the body and guide HER2-targeted therapies for patients. We therefore aimed to develop a HER2-targeted peptide probe for breast cancer imaging. A novel single-photon emission computed tomography (SPECT) imaging probe, (99m)Tc-HYNIC-H6F, was prepared and then evaluated in breast cancer animal models...
January 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28104682/out-ranking-brca1-in-mutation-carriers
#14
REVIEW
Emma Nolan, Geoffrey J Lindeman, Jane E Visvader
Beyond prophylactic mastectomy, there are currently very few options available to BRCA1 mutation carriers to help reduce their risk of developing breast cancer. An effective prevention therapy therefore remains a pressing area of need. Accumulating evidence points to amplification of the progesterone signaling axis in precancerous tissue from BRCA1 mutation carriers. Given that RANKL is an important paracrine mediator of hormonal signaling in breast tissue, there has been considerable interest in exploring a potential role for this pathway in oncogenesis...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28104566/targeting-epidermal-growth-factor-receptor-in-triple-negative-breast-cancer-new-discoveries-and-practical-insights-for-drug-development
#15
REVIEW
Ricardo Costa, Ami N Shah, Cesar A Santa-Maria, Marcelo R Cruz, Devalingam Mahalingam, Benedito A Carneiro, Young Kwang Chae, Massimo Cristofanilli, William J Gradishar, Francis J Giles
Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC...
January 5, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28103826/tracking-the-origin-of-simultaneous-endometrial-and-ovarian-cancer-by-next-generation-sequencing-a-case-report
#16
Nadejda Valtcheva, Franziska M Lang, Aurelia Noske, Eleftherios P Samartzis, Anna-Maria Schmidt, Elisa Bellini, Daniel Fink, Holger Moch, Markus Rechsteiner, Konstantin J Dedes, Peter J Wild
BACKGROUND: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. CASE PRESENTATION: In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28102883/exploring-prognostic-factors-for-her2-positive-metastatic-breast-cancer-a-retrospective-cohort-study-in-a-major-swiss-hospital
#17
Lilian Bringolf, Bernhard Pestalozzi, Daniel Fink, Konstantin Dedes
BACKGROUND: Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment. PATIENTS AND METHODS: This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81)...
January 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28101782/the-antineoplastic-drug-trastuzumab-dysregulates-metabolism-in-ipsc-derived-cardiomyocytes
#18
Brian M Necela, Bianca C Axenfeld, Daniel J Serie, Jennifer M Kachergus, Edith A Perez, E Aubrey Thompson, Nadine Norton
BACKGROUND: The targeted ERBB2 therapy, trastuzumab, has had a tremendous impact on management of patients with HER2+ breast cancer, leading to development and increased use of further HER2 targeted therapies. The major clinical side effect is cardiotoxicity but the mechanism is largely unknown. On the basis that gene expression is known to be altered in multiple models of heart failure, we examined differential gene expression of iPSC-derived cardiomyocytes treated at day 11 with the ERBB2 targeted monoclonal antibody, trastuzumab for 48 h and the small molecule tyrosine kinase inhibitor of EGFR and ERBB2...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28101463/development-of-a-novel-human-single-chain-antibody-against-egfrviii-antigen-by-phage-display-technology
#19
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Bahman Akbari, Shiva Ahdi Khosroshahi
Purpose: EGFRvIII as the most common mutant variant of the epidermal growth factor receptor is resulting from deletion of exons 2-7 in the coding sequence and junction of exons 1 and 8 through a novel glycine residue. EGFRvIII is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. The aim of the present study was identification of a novel single chain antibody against EGFRvIII as a promising target for cancer therapy. Methods: In this study, a synthetic peptide corresponding to EGFRvIII protein was used for screening a naive human scFv phage library...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101374/arginine-methylation-of-usp9x-promotes-its-interaction-with-tdrd3-and-its-anti-apoptotic-activities-in-breast-cancer-cells
#20
Nithya Narayanan, Zhihao Wang, Ling Li, Yanzhong Yang
The Tudor domain-containing proteins are characterized by their specific interactions with methylated protein motifs, including methyl-arginines and methyl-lysines. The Tudor domain-containing protein 3 (TDRD3) is one of the major methyl-arginine effector molecules that recognizes methylated arginine residues on histones and the C-terminal domain of RNA polymerase II, and activates transcription. However, majority of the cellular TDRD3 localizes to the cytoplasm and its functions there are still elusive. Here, we have identified ubiquitin-specific protease 9 X-linked (USP9X) as a TDRD3-interacting protein by GST (glutathione S-transferase) pull-down and co-immunoprecipitation...
2017: Cell Discovery
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