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https://www.readbyqxmd.com/read/29138558/%C3%AE-v%C3%AE-3-integrin-targeted-micellar-mertansine-prodrug-effectively-inhibits-triple-negative-breast-cancer-in-vivo
#1
Ping Zhong, Xiaolei Gu, Ru Cheng, Chao Deng, Fenghua Meng, Zhiyuan Zhong
Antibody-mertansine (DM1) conjugates (AMCs) are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs). Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29137420/anti-angiogenic-and-anti-tumor-effects-of-metronomic-use-of-novel-liposomal-zoledronic-acid-depletes-tumor-associated-macrophages-in-triple-negative-breast-cancer
#2
Xin-Jun Cai, Zeng Wang, Jia-Wei Cao, Jian-Jun Ni, Ying-Ying Xu, Jun Yao, Hong Xu, Fang Liu, Gao-Yi Yang
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137378/trastuzumab-distribution-in-an-in-vivo-and-in-vitro-model-of-brain-metastases-of-breast-cancer
#3
Tori B Terrell-Hall, Mohamed Ismail Nounou, Fatema El-Amrawy, Jessica I G Griffith, Paul R Lockman
Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of (125)I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135104/clinicopathological-and-prognostic-significance-of-cyclin-d1-amplification-in-patients-with-breast-cancer-a-meta-analysis
#4
Qi He, Jingxun Wu, Xin-Li Liu, Yi-Han Ma, Xiao-Ting Wu, Wen-Yi Wang, Han-Xiang An
PURPOSE: Cyclin D1 plays a critical role in tumorigenesis and the regulation of the G1/S transition in the cell cycle. The relationship between cyclin D1 amplification and clinicopathological parameters in patients with breast cancer remains controversial and its impact on survival outcome is not completely clear. We conducted a meta-analysis to investigate the associations between cyclin D1 gene amplification and certain clinicopathological characteristics and the prognosis in breast cancer...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29133799/hit-and-run-epigenetic-editing-prevents-senescence-entry-in-primary-breast-cells-from-healthy-donors
#5
Emily A Saunderson, Peter Stepper, Jennifer J Gomm, Lily Hoa, Adrienne Morgan, Michael D Allen, J Louise Jones, John G Gribben, Tomasz P Jurkowski, Gabriella Ficz
Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129754/cd44-targeting-hyaluronic-acid-coated-lapatinib-nanocrystals-foster-the-efficacy-against-triple-negative-breast-cancer
#6
Satish Agrawal, Monika Dwivedi, Hafsa Ahmad, Sangappa Basanna Chadchan, Abhishek Arya, Roshan Sikandar, Shweta Kaushik, Kalyan Mitra, Rajesh Kumar Jha, Anil Kumar Dwivedi
Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than its counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs not only increased the residence time of LPT, but also targeted the tumor, reduced the tumor burden, and increased overall survival...
November 9, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29124779/prenatal-diethylstilbestrol-exposure-and-cancer-risk-in-women
#7
Rebecca Troisi, Elizabeth E Hatch, Linda Titus, William Strohsnitter, Mitchell H Gail, Dezheng Huo, Ervin Adam, Stanley J Robboy, Marianne Hyer, Robert N Hoover, Julie R Palmer
In the Diethylstilbestrol [DES] Combined Cohort Follow-up, the age- and calendar-year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51-70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01-1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79-1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21-4.34) and the adjusted HR for comparison with unexposed women was 7...
November 10, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29123254/implications-of-aging-and-the-endoplasmic-reticulum-unfolded-protein-response-on-the-molecular-modality-of-breast-cancer
#8
REVIEW
Rinki Minakshi, Safikur Rahman, Arif Tasleem Jan, Ayyagari Archana, Jihoe Kim
The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca(2+). The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death...
November 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29117945/adipocytes-sequester-and-metabolize-the-chemotherapeutic-daunorubicin
#9
Xia Sheng, Jean-Hugues Parmentier, Jonathan Tucci, Hua Pei, Omar Cortez-Toledo, Christina M Dieli-Conwright, Matthew J Oberley, Michael Neely, Etan Orgel, Stan G Louie, Steven D Mittelman
Obesity is associated with poorer outcome for many cancers. Previously, we observed that adipocytes protect acute lymphoblastic leukemia (ALL) cells from the anthracycline, daunorubicin. In this study, it is determined whether adipocytes clear daunorubicin from the tumor microenvironment (TME). Intracellular daunorubicin concentrations were evaluated using fluorescence. Daunorubicin and its largely inactive metabolite, daunorubicinol, were analytically measured in media, cells, and tissues using liquid chromatography/mass spectrometry (LC/MS)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29115548/frankincense-pine-needle-and-geranium-essential-oils-suppress-tumor-progression-through-the-regulation-of-the-ampk-mtor-pathway-in-breast-cancer
#10
Peng Ren, Xiang Ren, Lei Cheng, Lixin Xu
BC (BC), as the most common malignancy in women worldwide, is associated with high morbidity and mortality. However, chemoresistance and toxicity are the main causes that limit the success of treatment in aggressive BC cases. Thus, there is a vital need to identify and develop novel therapeutic agents. Frankincense, pine needle and geranium essential oils have been reported to play critical biological activities in cancer. However, to the best of our knowledge whether frankincense, pine needle and geranium essential oils have any effect on the progression of BC in MCF-7 cells remains unclear...
November 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29115416/annexin-a2-and-cancer-a-systematic-review
#11
Maria V Christensen, Claus K Høgdall, Kirsten M Jochumsen, Estrid V S Høgdall
Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using PubMed. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma, prostate cancer and urothelial carcinoma were evaluated...
November 8, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29115408/salidroside-could-enhance-the-cytotoxic-effect-of-l%C3%A2-ohp-on-colorectal-cancer-cells
#12
Xiaoming Shi, Wei Zhao, Yongbin Yang, Shengchun Wu, Bonan Lv
Evidence has suggested that salidroside inhibits the proliferation and invasion of renal clear cell, lung, breast, and colon cancer. However, effect of salidroside on colorectal cancer (CRC) cells against oxaliplatin (L‑OHP) resistance remains unclear. In the present study, the CRC HT‑29 cell line and L‑OHP resistance HT‑29/L‑OHP cell line were used to evaluate the effect, and mechanism of salidroside on L‑OHP resistance. The results demonstrated that the activity of HT‑29 cells was lower compared with that of HT‑29/L‑OHP cells following L‑OHP intervention, and was accompanied with varied expression levels of drug resistant proteins...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113324/unfolded-protein-response-signaling-impacts-macrophage-polarity-to-modulate-breast-cancer-cell-clearance-and-melanoma-immune-checkpoint-therapy-responsiveness
#13
David R Soto-Pantoja, Adam S Wilson, Kenysha Yj Clear, Brian Westwood, Pierre L Triozzi, Katherine L Cook
The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization. Specifically, PERK targeting enhanced macrophage proliferation and macrophage-mediated killing but not GRP78 or IRE1. Targeting UPR in cancer cells also differentially affected macrophage cytolytic capacity. Tumoral IRE1 or GRP78 inhibition enhanced macrophage-mediated cancer cell clearance. Conditioned media from GRP78-silenced cancer cells caused reciprocal regulation of CD80 and CD206, suggesting control of plasticity by secreted factors...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108265/cellular-inhibitor-of-apoptosis-protein-2-promotes-the-epithelial-mesenchymal-transition-in-triple-negative-breast-cancer-cells-through-activation-of-the-akt-signaling-pathway
#14
Su Ji Jo, Pil-Gu Park, Hye-Ran Cha, Sung Gwe Ahn, Min Jung Kim, Hyemi Kim, Ja Seung Koo, Joon Jeong, Jeon Han Park, Seung Myung Dong, Jae Myun Lee
Triple-negative breast cancer (TNBC) represents approximately 10-17% of all breast cancers, and patients with TNBC show a poorer short-term prognosis than patients with other types of breast cancer. TNBCs also have a higher tendency for early distant metastasis and cancer recurrence due to induction of the epithelial-mesenchymal transition (EMT). Several recent reports have suggested that inhibitor of apoptosis (IAP) proteins function as regulators of the EMT. However, the roles of these proteins in TNBC are not clear...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104950/-89-zr-cobalamin-pet-tracer-synthesis-cellular-uptake-and-use-for-tumor-imaging
#15
Akhila N W Kuda-Wedagedara, Jayme L Workinger, Ebba Nexo, Robert P Doyle, Nerissa Viola-Villegas
Vitamin B12, or cobalamin (Cbl), is an essential nutrient. Acquisition, transport, and cellular internalization of Cbl are dependent on specific binding proteins and associated receptors. The circulating transport protein transcobalamin (TC) promotes cellular uptake via binding to specific receptors such as CD320, a receptor upregulated in several cancer cell lines. In this study, we report the successful synthesis of (89)Zirconium-labeled Cbl that was derivatized with desferrioxamine ((89)Zr-Cbl). We document the purity of the tracer and its binding to TC compared with that of unmodified cyano-Cbl (CN-Cbl)...
October 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29101636/lyp-1-conjugated-nanoparticles-for-magnetic-resonance-imaging-of-triple-negative-breast-cancer
#16
Abedelnasser Abulrob, Slavisa Corluka, Barbara Blasiak, B Gino Falonne, Dragana Ponjevic, John Matyas, Boguslaw Tomanek
PURPOSE: Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, or Her2/neu. Both diagnosis and treatment of TNBC remain a clinical challenge. LyP-1 is a cyclic 9 amino acid peptide that can bind to breast cancer cells. The goal of this study was to design and characterize LyP-1 conjugated to fluorescent iron oxide nanoparticles (LyP-1-Fe3O4-Cy5.5) as a contrast agent for improved and specific magnetic resonance imaging (MRI) in a preclinical model of TNBC...
November 3, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29100362/the-prognostic-significance-of-combined-androgen-receptor-e-cadherin-ki67-and-ck5-6-expression-in-patients-with-triple-negative-breast-cancer
#17
Barbara Adamo, Giuseppina Rosaria Rita Ricciardi, Antonio Ieni, Tindara Franchina, Carmine Fazzari, Maria Vita Sanò, Giuseppe Angelico, Caruso Michele, Giovanni Tuccari, Vincenzo Adamo
Background: Triple Negative Breast Cancer (TNBC) represents a heterogeneous group of tumors with poor prognosis owing to aggressive tumor biology and lack of targeted therapies. No clear prognostic biomarkers have been identified to date for this subgroup. Materials and Methods: In this retrospective study we evaluated the prognostic role of 4 different molecular determinants, including androgen receptor (AR), E-cadherin (CDH1), Ki67 index, and basal cytokeratins (CKs) 5/6, in a cohort of 99 patients with TNBC...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100335/breast-cancer-induced-nociceptor-aberrant-growth-and-collateral-sensory-axonal-branching
#18
Matt Austin, Laura Elliott, Niovi Nicolaou, Anna Grabowska, Richard P Hulse
The tumour and neuron interaction has a significant impact upon disease progression and the patients quality of life. In breast cancer patients, it is known that there is an interaction between the tumour microenvironment and the sensory neurons to influence the progression of cancer as well as pain, though these mechanisms still need to be clearly defined. Here it is demonstrated that in a rodent orthotopic model of breast cancer (MDA MB 231) there was an increase in nerve fibre innervation into the tumour microenvironment (protein gene product 9...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29084054/columnar-cell-lesion-and-apocrine-hyperplasia-of-the-breast-is-there-a-common-origin-the-role-of-prolactin-induced-protein
#19
Amedeo Sciarra, Gianluca Lopez, Chiara Corti, Letterio Runza, Giulia Ercoli, Arturo Bonometti, Luca Despini, Concetta Blundo, Donatella Gambini, Nicola Fusco
Noninvasive breast lesions encompass a heterogeneous group of risk indicators and nonobligate precursors of breast cancer, such as apocrine hyperplasia (AH) and columnar cell lesions (CCLs). Given the different expression of ER and ER-regulated genes in AH and CCL, these two alterations are currently considered discrete conditions. However, whether they share early biologic changes is not clear to date. Here, we sought to define the clinicopathologic and immunohistochemical features of a prospective series of combined lesions made up by CCLs and AH forming a continuum within single terminal duct-lobular units...
October 27, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29083228/rutin-as-a-novel-c-met-inhibitory-lead-for-the-control-of-triple-negative-breast-malignancies
#20
Heba E Elsayed, Hassan Y Ebrahim, Mohamed M Mohyeldin, Abu Bakar Siddique, Amel M Kamal, Eman G Haggag, Khalid A El Sayed
Triple negative breast cancer (TNBC) has high metastatic and mortality potential and lacks effective and selective therapeutic options. Aberrant dysregulation of the receptor tyrosine kinase c-Met promotes TNBC progression, motility and survival and therefore considered a valid therapeutic target. Among various identified anticancer agents, plant polyphenols (PPs) including flavonoids, have been shown to be safe and proven for their antitumor activity through modulating diverse macromolecular targets. This study reports the bioassay-guided identification of the common flavonol glycoside rutin as breast cancer cell proliferation, migration and invasion inhibitor...
October 30, 2017: Nutrition and Cancer
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