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https://www.readbyqxmd.com/read/28731466/interaction-of-galectin-3-with-muc1-on-cell-surface-promotes-egfr-dimerization-and-activation-in-human-epithelial-cancer-cells
#1
Tushar Piyush, Anisha R Chacko, Paulina Sindrewicz, John Hilkens, Jonathan M Rhodes, Lu-Gang Yu
Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#2
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28725490/muc1-o-glycosylation-contributes-to-anoikis-resistance-in-epithelial-cancer-cells
#3
Tushar Piyush, Jonathan M Rhodes, Lu-Gang Yu
Anoikis is a fundamental cellular process for maintaining tissue homeostasis. Resistance to anoikis is a hallmark of oncogenic epithelial-mesenchymal transition and is a pre-requisite for metastasis. Previous studies have revealed that the heavily glycosylated mucin protein MUC1, which is overexpressed in all types of epithelial cancer cells, prevents anoikis initiation in response to loss of adhesion. This effect of MUC1 is largely attributed to its extracellular domain that provides cell surface anoikis-initiating molecules with a 'homing' microenvironment...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28720669/muc1-mediated-metabolic-alterations-regulate-response-to-radiotherapy-in-pancreatic-cancer
#4
Venugopal Gunda, Joshua J Souchek, Jaime Abrego, Surendra K Shukla, Gennifer D Goode, Enza Vernucci, Aneesha Dasgupta, Nina CHaika, Ryan J King, Sicong Li, Shuo Wang, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K Singh
Purpose: MUC1, an oncogene overexpressed in multiple solid tumors including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models. <p>Experimental design: We used MUC1 knockdown and overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response and metabolomic evaluations...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28717171/the-aspirin-metabolite-salicylate-inhibits-lysine-acetyltransferases-and-muc1-induced-epithelial-to-mesenchymal-transition
#5
Harvey R Fernandez, Sara K Lindén
MUC1 is a transmembrane mucin that can promote cancer progression, and its upregulation correlates with a worse prognosis in colon cancer. We examined the effects of overexpression of MUC1 in colon cancer cells, finding that it induced epithelial to mesenchymal transition (EMT), including enhanced migration and invasion, and increased Akt phosphorylation. When the clones were treated with the aspirin metabolite salicylate, Akt phosphorylation was decreased and EMT inhibited. As the salicylate motif is necessary for the activity of the lysine acetyltransferase (KAT) inhibitor anacardic acid, we hypothesized these effects were associated with the inhibition of KAT activity...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710001/congenital-lingual-cyst-expression-of-muc-protein-and-report-of-a-new-case
#6
G Martínez-Mata, D Inda-Cunningham, J A Medina-López, R Pacheco-Santiesteban, H Monreal-Romero
Lingual congenital cysts are uncommon lesions that alter the functions of speech, swallowing and breathing when they have considerable dimension. They usually appear from birth and increase in size gradually in childhood and adolescence. While there are a considerable number of case reports, the nomenclature and origin of this lesion are controversial. Congenital lingual cysts are composed of an epithelial lining that can show heterogeneous histological features, such as globed, ciliated, squamous and parietal cells, while the wall presents mature connective tissue and eventually smooth muscle...
July 12, 2017: Journal of Stomatology, Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28707580/doxorubicin-loaded-micelle-targeting-muc1-a-potential-therapeutics-for-triple-negative-breast-cancer-treatment
#7
Supang Khondee, Chuda Chittasupho, Singkome Tima, Songyot Anuchapreeda
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease associated with poor prognosis and lack of validated targeted therapy. Thus chemotherapy is a main adjuvant treatment for TNBC patients, but it associates with severe toxicities. For a better treatment outcome, we developed an alternative therapeutic, doxorubicin (DOX)-loaded micelles targeting human mucin1 protein (MUC1) that is less toxic, more effective and targeted to TNBC. METHODS: From many candidate peptides, QNDRHPR-GGGSK (QND) and HSQLPQV-GGGSK (HSQ), were identified computationally, synthesized and purified using solid phase peptide synthesis and semi-preparative HPLC...
July 12, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28706419/intestinal-anti-inflammatory-activity-of-ground-cherry-physalis-angulata-l-standardized-co2-phytopharmaceutical-preparation
#8
Luiz Domingues Almeida Junior, Ana Elisa Valencise Quaglio, Celso Acácio Rodrigues de Almeida Costa, Luiz Claudio Di Stasi
AIM: To investigate the effects of Ground Cherry (Physalis angulata L.) standardized supercritical CO2 extract in trinitrobenzenesulphonic acid (TNBS) model of rat intestinal inflammation. METHODS: The animals were divided into groups that received vehicle or P. angulata extract (PACO2) orally at the doses 25, 50 and 100 mg/kg daily by 5 d before TNBS damage. Protective effects of PACO2 were assessed by macroscopic analysis, biochemical determinations of the levels of myeloperoxidase (MPO), alkaline phosphatase (ALP), glutathione and cytokines (such as INF-γ, IL-1β, IL-6, IL-10 and TNF-α), gene expression evaluation (including Hsp70, heparanase, NF-κB, mitogen-activated protein kinases (Mapk) 1, 3, 6 and 9, and the mucins genes Muc 1, 2, 3 and 4) and histopathological studies using optical, and electronic (transmission and scanning) microscopy...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28699810/a-balanced-level-of-profilin-1-promotes-stemness-and-tumor-initiating-potential-of-breast-cancer-cells
#9
Chang Jiang, Zhijie Ding, Marion Joy, Souvik Chakraborty, Su Hyeong Kim, Ralph Bottcher, John Condeelis, Shivendra Singh, Partha Roy
Profilin-1 (Pfn1) is an important actin-regulatory protein that is downregulated in human breast cancer and when forcibly elevated, it suppresses the tumor-initiating ability of triple-negative breast cancer cells. In this study, we demonstrate that Pfn1 overexpression reduces the stem-like phenotype (a key biological feature associated with higher tumor-initiating potential) of MDA-MB-231 (MDA-231) triple-negative breast cancer cells. Interestingly, the stem-like trait of MDA-231 cells is also attenuated upon depletion of Pfn1...
July 12, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28697344/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#10
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Sarkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28697341/muc-king-with-hif-may-rewire-pyrimidine-biosynthesis-and-curb-gemcitabine-resistance-in-pancreatic-cancer
#11
Chi V Dang
In this issue of Cancer Cell, Singh and colleagues report a role for MUC1-induced HIF expression in rewiring ribose synthesis, which drives pyridimine production as a possible resistance mechanism to gemcitabine, adding to complexity and multiple paths to resistance.
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28697153/mucin-expression-in-the-esophageal-malignant-and-premalignant-states-a-systematic-review-and-meta-analysis
#12
Yaron Niv, Samuel B Ho, Ronnie Fass, Theodore Rokkas
BACKGROUND: Mucins are heavily glycosylated glycoproteins, synthesized by mucosal surfaces and have an important role in healthy state and malignant diseases. Change in mucins synthesis or secretion may be primary event or secondary to inflammation or carcinogenesis. AIM: The aim of this study is to assess the current knowledge about mucin expression in esophageal lesions, and to establish a role for different mucin expressions as prognostic markers. METHOD: English Medical literature searches were conducted for "mucin" and "esophagus...
July 10, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28697053/postoperative-adjuvant-therapy-for-resectable-pancreatic-cancer-with-gemcitabine-and-adoptive-immunotherapy
#13
Hiroto Matsui, Shoichi Hazama, Kazuhiko Sakamoto, Yoshitaro Shindo, Shinsuke Kanekiyo, Masao Nakashima, Satoshi Matsukuma, Yoshihiro Tokuhisa, Michihisa Iida, Nobuaki Suzuki, Kiyoshi Yoshimura, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Masaaki Oka, Hiroaki Nagano
OBJECTIVES: We previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)-expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer. METHODS: A total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM...
July 11, 2017: Pancreas
https://www.readbyqxmd.com/read/28693233/pre-operative-evaluation-of-circulating-kl-6-levels-as-a-biomarker-for-epithelial-ovarian-carcinoma-and-its-correlation-with-tumor-muc1-expression
#14
Sho Sato, Tomomi Kato, Kenji Abe, Tatsuya Hanaoka, Yuri Yano, Akira Kurosaki, Masanori Yasuda, Tetsuo Sekino, Keiichi Fujiwara, Kosei Hasegawa
Krebs von den Lungen-6 (KL-6), a mucinous sialylated sugar chain on human mucin-1 glycoprotein (MUC1), is a diagnostic marker for interstitial lung diseases. Furthermore, elevated serum KL-6 levels have been observed in certain malignant tumor types of epithelial origin. The expression of MUC1 has been observed in patients with epithelial ovarian cancer (EOC) and is considered a potential therapeutic target. In the present study, KL-6 serum levels were investigated in patients clinically suspected of having malignant ovarian tumors...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692035/role-of-integrin-linked-kinase-in-regulating-the-protein-stability-of-the-muc1-c-oncoprotein-in-pancreatic-cancer-cells
#15
H-L Huang, H-Y Wu, P-C Chu, I-L Lai, P-H Huang, S K Kulp, S-L Pan, C-M Teng, C-S Chen
MUC1-C overexpression has been associated with the progression of pancreatic tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3 target gene, STAT3 plays a major role in regulating MUC1-C expression. In this study, we report an alternative mechanism by which integrin-linked kinase (ILK) post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. We found that ILK acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28687020/chemotherapy-administration-to-breast-cancer-patients-affects-extracellular-vesicles-thrombogenicity-and-function
#16
Anat Aharon, Anni Sabbah, Shahar Ben-Shaul, Hila Berkovich, David Loven, Benjamin Brenner, Gil Bar-Sela
Breast cancer (BC) is the most prevalent type of malignancy in women. Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles. STUDY AIMS: To elucidate the effects of chemotherapy administration on BC patients' EVs characteristics and their effects on endothelial cells (EC) functions. METHODS: EVs were isolated from the blood samples of 54 BC patients treated by chemotherapy (25 neo-adjuvant, 29 adjuvant) and from 20 healthy women (control group)...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28680538/a-tumor-specific-antibody-to-aid-breast-cancer-screening-in-women-with-dense-breast-tissue
#17
Lopamudra Das Roy, Lloye M Dillon, Ru Zhou, Laura J Moore, Chad Livasy, Joe M El-Khoury, Rahul Puri, Pinku Mukherjee
Screening for breast cancer has predominantly been done using mammography. Unfortunately, mammograms miss 50% cancers in women with dense breast tissue. Multi-modal screenings offer the best chance of enhancing breast cancer screening effectiveness. We evaluated the use of TAB004, an antibody that recognizes the tumor form of the glycoprotein MUC1 (tMUC1), to aid early detection of breast cancer. Our experimental approach was to follow tMUC1 from the tissue into circulation. We found that 95% of human breast cancer tissues across all subtypes stained positive for TAB004...
March 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28679396/identification-of-new-muc1-epitopes-using-hla-transgenic-animals-implication-for-immunomonitoring
#18
Tanja Scheikl-Gatard, Caroline Tosch, François Lemonnier, Ronald Rooke
BACKGROUND: The success of immunotherapeutics in oncology and the search for further improvements has prompted revisiting the use of cancer vaccines. In this context, knowledge of the immunogenic epitopes and the monitoring of the immune response cancer vaccines generate are essential. MUC1 has been considered one of the most important tumor associated antigen for decades. METHODS: To identify HLA-restricted MUC1 peptides we used eight human MHC class I transgenic mouse lines, together covering more than 80% of the human population...
July 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28675699/immunization-with-a-synthetic-human-muc1-glycopeptide-vaccine-against-tumor-associated-muc1-breaks-tolerance-in-human-muc1-transgenic-mice
#19
Horst Kunz, Natascha Stergiou, Markus Glaffig, Helmut Jonuleit, Edgar Schmitt
Breaking the tolerance is crucial for an effective tumor immunotherapy. We showed that vaccines containing tumor-associated human MUC1 glycopeptides induce strong humoral anti-tumor responses in mice. The question remained whether such vaccines work in humans, in systems where huMUC1 is a self-antigen. To clarify the question, mice transgenic in expressing huMUC1, mimicking the self-tolerant environment, and wild-type mice were vaccinated with a synthetic vaccine. This vaccine comprised STn and Tn antigens bound to a MUC1 tandem repeat peptide coupled to Tetanus Toxoid...
July 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28671278/the-application-of-aptamer-5tr1-in-triple-negative-breast-cancer-target-therapy
#20
Shangyang Luo, Shouman Wang, Na Luo, Feiyu Chen Chun Hu, Kejing Zhang
Chemotherapy is one of the standard strategies for treatment of breast cancer. Adriamycin (Dox) is a first-line chemotherapy agent for breast cancer. However, the gastrointestinal reactions, myocardial toxicity and other side effects caused by Dox due to its un-specific cytotoxicity limit the clinical treatment effect. To address this need, aptamer has been regarded as an ideal target molecular carrier. In the present study, we selected an aptamer 5TR1 that can specifically bind to the MUC1 protein which has been regarded as an important tumor biomarker, as well as a potential target in anticancer therapies...
July 3, 2017: Journal of Cellular Biochemistry
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