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https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#1
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#2
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29777404/randomized-trial-comparing-resection-of-primary-tumor-with-no-surgery-in-stage-iv-breast-cancer-at-presentation-protocol-mf07-01
#3
Atilla Soran, Vahit Ozmen, Serdar Ozbas, Hasan Karanlik, Mahmut Muslumanoglu, Abdullah Igci, Zafer Canturk, Zafer Utkan, Cihangir Ozaslan, Turkkan Evrensel, Cihan Uras, Erol Aksaz, Aykut Soyder, Umit Ugurlu, Cavit Col, Neslihan Cabioglu, Betül Bozkurt, Ali Uzunkoy, Neset Koksal, Bahadir M Gulluoglu, Bulent Unal, Can Atalay, Emin Yıldırım, Ergun Erdem, Semra Salimoglu, Atakan Sezer, Ayhan Koyuncu, Gunay Gurleyik, Haluk Alagol, Nalan Ulufi, Uğur Berberoglu, Mustafa Dulger, Omer Cengiz, Efe Sezgin, Ronald Johnson
BACKGROUND: The MF07-01 trial is a multicenter, phase III, randomized, controlled study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone for treatment-naïve stage IV breast cancer (BC) patients. METHODS: At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. RESULTS: The trial enrolled 274 patients: 138 in the LRT group and 136 in the ST group...
May 17, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#4
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29777274/the-natural-agent-4-vinylphenol-targets-metastasis-and-stemness-features-in-breast-cancer-stem-like-cells
#5
Hoi-Wing Leung, Chun-Hay Ko, Grace Gar-Lee Yue, Ingrid Herr, Clara Bik-San Lau
BACKGROUND AND PURPOSE: Cancer stem-like cells (CSC) are regarded as the source of tumour origins, metastasis and drug resistance, and limits current treatment regimens. Previously, we reported the first study of the anti-angiogenic and anti-tumour activities of 4-vinylphenol. To further examine the therapeutic role of 4-vinylphenol, the inhibitory effects of 4-vinylphenol on cancer stemness, drug resistance and metastasis in breast cancer were investigated in the present study. STUDY DESIGN AND METHODS: We enriched parental MDA-MB-231 cells with CSCs in serum-free medium to give spheroids...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29777109/tak1-mediates-microenvironment-triggered-autocrine-signals-and-promotes-triple-negative-breast-cancer-lung-metastasis
#6
Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777007/development-of-64-cu-nota-trastuzumab-for-her2-targeting-radiopharmaceutical-with-improved-pharmacokinetics-for-human-study
#7
Sang-Keun Woo, Su Jin Jang, Min-Jung Seo, Ju Hui Park, Byoung Soo Kim, Eun Jung Kim, Yong Jin Lee, Tae Sup Lee, Gwang Il An, In Ho Song, Youngho Seo, Kwang Il Kim, Joo Hyun Kang
Purpose The purpose of this study was to develop 64 Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2. Methods Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64 Cu. Serum stability and immunoreactivity of 64 Cu-NOTA-trastuzumab were tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer xenograft model (BT-474). Internal dosimetry of experimental animals was performed using the image-based approach with the Monte Carlo N-Particle Code...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29775617/preoperative-lymphocyte-to-monocyte-ratio-predicts-breast-cancer-outcome-a-meta-analysis
#8
REVIEW
Ru-Jin Hu, Jian-Ying Ma, Qin Liu, Jing Zhou, Gang Liu
AIM: To assess the prognostic value of the preoperative lymphocyte-to-monocyte ratio (LMR) in patients with breast cancer (BC). METHODS: Relevant studies were systematically retrieved from the online Cochrane, MEDLINE, EMBASE and CNKI databases published until February 2018. The end points were overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. Meta-analysis was performed using hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) as effect measures...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29775160/site-specific-expression-of-amine-oxidases-in-breast-cancer-metastases
#9
Yoon Jin Cha, Woo Hee Jung, Ja Seung Koo
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29774130/targeting-invadopodia-mediated-breast-cancer-metastasis-by-using-abl-kinase-inhibitors
#10
Tomer Meirson, Alessandro Genna, Nikola Lukic, Tetiana Makhnii, Joel Alter, Ved P Sharma, Yarong Wang, Abraham O Samson, John S Condeelis, Hava Gil-Henn
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774079/long-non-coding-rnas-ac026904-1-and-uca1-a-one-two-punch-for-tgf-%C3%AE-induced-snai2-activation-and-epithelial-mesenchymal-transition-in-breast-cancer
#11
Guo-Yin Li, Wei Wang, Jian-Yong Sun, Bo Xin, Xiang Zhang, Ting Wang, Qian-Feng Zhang, Li-Bo Yao, Hua Han, Dai-Ming Fan, An-Gang Yang, Lin-Tao Jia, Lei Wang
Transforming growth factor-β (TGF-β) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-β-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-β treated and untreated breast cancer cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29774078/targeting-intracellular-mmps-efficiently-inhibits-tumor-metastasis-and-angiogenesis
#12
Yaqi Lv, Xiangmei Zhao, Lidan Zhu, Sijia Li, Qingqing Xiao, Wei He, Lifang Yin
Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra...
2018: Theranostics
https://www.readbyqxmd.com/read/29774072/twist-promotes-tumor-metastasis-in-basal-like-breast-cancer-by-transcriptionally-upregulating-ror1
#13
Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P Zhou, Jian Shi, Tiebang Kang
Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins...
2018: Theranostics
https://www.readbyqxmd.com/read/29772993/shoulder-lesion-in-a-69-year-old-woman
#14
Andrew J Hayden, Srinivas Kolla, Adele L Boskey, Steven Burekhovich, Chuanyong Lu, Michael Stracher, Aditya V Maheshwari
Milwaukee Shoulder Syndrome (MSS) is a painful progressive arthropathy in which hydroxyapatite crystal deposition in synovial tissue induces lysosomal release of collagenase and neutral proteases. These enzymes are destructive to periarticular tissue, including the synovium, articular cartilage, rotator cuff muscles, and the intrasynovial cortical bone. MSS predominantly occurring in women (90%) over the age of 70 years of age with a clinical history marked by recurrent joint effusions and pain, which classically worsens at night...
2018: Journal of Long-term Effects of Medical Implants
https://www.readbyqxmd.com/read/29772510/dkk1-and-kremen-expression-predicts-the-osteoblastic-response-to-bone-metastasis
#15
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29772457/in-vitro-and-in-vivo-metabolic-investigation-of-the-palbociclib-by-uhplc-q-tof-ms-ms-and-in-silico-toxicity-studies-of-its-metabolites
#16
Balasaheb B Chavan, Shristy Tiwari, Shankar G, Rakesh D Nimbalkar, Prabha Garg, Srinivas R, M V N Kumar Talluri
Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug...
May 14, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29770955/laptm4b-gene-copy-number-gain-is-associated-with-inferior-response-to-anthracycline-based-chemotherapy-in-hormone-receptor-negative-breast-carcinomas
#17
Orsolya Rusz, Orsolya Papp, Laura Vízkeleti, Béla Ákos Molnár, Kristóf Csaba Bende, Gábor Lotz, Balázs Ács, Zsuzsanna Kahán, Tamás Székely, Ágnes Báthori, Csilla Szundi, Janina Kulka, Zoltán Szállási, Anna-Mária Tőkés
PURPOSE: To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas. PATIENTS AND METHODS: Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77...
May 16, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29770894/efficacy-of-punarnavine-in-restraining-organ-specific-tumour-progression-in-4t1-induced-murine-breast-tumour-model
#18
Gilcy George Kallivalappil, Girija Kuttan
Most of the breast cancer deaths occur when cancer cells depart from their tumour of origin and spread systemically and colonise distant organs. The present study was to find out whether punarnavine, the quinolizidine alkaloid, with already proven antimetastatic effect on spontaneous B16F10 pulmonary metastasis has got any effect on a drastic organ-specific breast cancer spread. For the study, we selected a syngenic mouse 4T1 breast tumour model that mimics stage four of human breast cancer. The metastatic progression of 4T1 to lymph nodes, lungs, and liver was reduced by punarnavine (40 mg/kg body weight) administration in BALB/c mice...
May 17, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29770285/large-non-enhancing-breast-cancer-on-breast-magnetic-resonance-imaging-a-case-report
#19
Johannes Peters, Wei Che Tsai, Gudrun Peters
A 55-year-old female presented with vague symptoms in the lateral left breast. Digital breast tomosynthesis and breast ultrasound showed no focal lesion, and magnetic resonance imaging (MRI) was subsequently performed. No suspicious enhancement was seen on MRI; in particular, no suspicious lesion was seen in the area of clinical concern. In view of persisting focal mastalgia and vague parenchymal changes in the symptomatic area on repeat targeted ultrasound, a core biopsy was performed. Final pathology after left mastectomy with axillary clearance showed a 42 mm grade 2 invasive ductal carcinoma...
March 15, 2018: Curēus
https://www.readbyqxmd.com/read/29769179/rna-profiles-of-circulating-tumor-cells-and-extracellular-vesicles-for-therapy-stratification-of-metastatic-breast-cancer-patients
#20
Corinna Keup, Pawel Mach, Bahriye Aktas, Mitra Tewes, Hans-Christian Kolberg, Siegfried Hauch, Markus Sprenger-Haussels, Rainer Kimmig, Sabine Kasimir-Bauer
BACKGROUND: Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS: Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points...
May 16, 2018: Clinical Chemistry
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