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https://www.readbyqxmd.com/read/29349448/a-study-on-platinum-iv-species-containing-an-estrogen-receptor-modulator-to-reverse-tamoxifen-resistance-of-breast-cancer
#1
Weiwei Hu, Jian Zhao, Wuyang Hua, Shaohua Gou
Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and platinum(ii) drugs were designed and synthesized for targeting estrogen receptors (ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity against breast cancer cells, but also reversed the tamoxifen resistance of TamR-MCF-7 cancer cells. Computational docking assays together with cellular uptake data demonstrated that the ER ligand portion of these conjugates plays a targeting role in ER-positive tumor cells and promotes the uptake of platinum via an estrogen receptor-mediated pathway...
January 19, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29348142/sema3c-drives-cancer-growth-by-transactivating-multiple-receptor-tyrosine-kinases-via-plexin-b1
#2
James W Peacock, Ario Takeuchi, Norihiro Hayashi, Liangliang Liu, Kevin J Tam, Nader Al Nakouzi, Nastaran Khazamipour, Tabitha Tombe, Takashi Dejima, Kevin Ck Lee, Masaki Shiota, Daksh Thaper, Wilson Cw Lee, Daniel Hf Hui, Hidetoshi Kuruma, Larissa Ivanova, Parvin Yenki, Ivy Zf Jiao, Shahram Khosravi, Alice L-F Mui, Ladan Fazli, Amina Zoubeidi, Mads Daugaard, Martin E Gleave, Christopher J Ong
Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition...
January 18, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29343199/cd204-expressing-tumor-associated-macrophages-are-associated-with-malignant-high-grade-and-hormone-receptor-negative-canine-mammary-gland-tumors
#3
Byung-Joon Seung, Ha-Young Lim, Jong-Il Shin, Hyun-Woo Kim, Seung-Hee Cho, Soo-Hyeon Kim, Jung-Hyang Sur
Tumor-associated macrophages (TAMs) are an important component of leukocyte infiltration in tumors. TAMs can be classified into M1 and M2 phenotypes. In the present study, the expression of CD204, an M2-polarized macrophage receptor, was investigated by immunohistochemistry in the area surrounding TAMs in 101 cases of canine mammary gland tumor (CMT). We examined the relationship between M2-polarized TAMs and malignancy, histological subtype, histological grade, molecular subtype, hormone receptor (HR) status, and clinical obesity indices...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29342502/antiphospholipid-antibodies-inhibit-trophoblast-toll-like-receptor-and-inflammasome-negative-regulators
#4
Melissa J Mulla, Ingrid C Weel, Julie A Potter, Stefan M Gysler, Jane E Salmon, Maria T S Peraçoli, Carla V Rothlin, Lawrence W Chamley, Vikki M Abrahams
OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. While these antibodies are heterogeneous, some anti-β2 GPI antibodies can activate human first trimester trophoblast TLR4 and NLRP3. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL-induced trophoblast inflammation. METHODS: Human trophoblast cells were treated with or without anti-β2 GPI aPL or control IgG in the presence or absence of the common TAM receptor ligand, GAS6, or the autophagy inducer, rapamycin...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29338742/m2-polarized-tumor-associated-macrophages-facilitated-migration-and-epithelial-mesenchymal-transition-of-hcc-cells-via-the-tlr4-stat3-signaling-pathway
#5
Rong-Rong Yao, Jing-Huan Li, Rui Zhang, Rong-Xin Chen, Yan-Hong Wang
BACKGROUND: M2-polarized macrophages are tumor-associated-macrophages (TAMs), which are important contents of tumor-infiltrating immune cells. Toll-like receptor 4 (TLR4) is a molecular biomarker of tumor aggressiveness and poor prognosis. Toll-like receptors (TLRs) have important roles in the immune system and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized macrophages...
January 16, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29336868/the-therapeutic-potential-of-targeting-the-peripheral-endocannabinoid-cb1-receptor-system
#6
REVIEW
Joseph Tam, Liad Hinden, Adi Drori, Shiran Udi, Shahar Azar, Saja Baraghithy
Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CB1R system in modulating the metabolism in several peripheral organs. We assess how eCBs, via activating the CB1R, contribute to obesity and regulate food intake...
January 11, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29336030/the-aryl-hydrocarbon-receptor-modulates-the-function-of-human-cd56bright-nk-cells
#7
Uriel Y Moreno-Nieves, David C Mundy, June Ho Shin, Kenric Tam, John B Sunwoo
Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions...
January 16, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29326185/enhancing-prescribing-of-guideline-recommended-medications-for-ischaemic-heart-diseases-a-systematic-review-and-meta-analysis-of-interventions-targeted-at-healthcare-professionals
#8
Thang Nguyen, Hoa Q Nguyen, Niken N Widyakusuma, Thao H Nguyen, Tam T Pham, Katja Taxis
OBJECTIVES: Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health outcomes in patients with IHDs. METHODS: We systematically searched PubMed and EMBASE for studies published between 1 January 2000 and 31 August 2017. We included original studies of interventions targeted at healthcare professionals to enhance prescribing guideline-recommended medications for IHDs...
January 10, 2018: BMJ Open
https://www.readbyqxmd.com/read/29324844/absence-of-myeloid-klf4-reduces-prostate-cancer-growth-with-pro-atherosclerotic-activation-of-tumor-myeloid-cells-and-infiltration-of-cd8-t-cells
#9
David J Barakat, Rahul Suresh, Theresa Barberi, Kenneth J Pienta, Brian W Simons, Alan D Friedman
The microenvironment of prostate cancer often includes abundant tumor-associated macrophages (TAMs), with their acquisition of an M2 phenotype correlating with local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2 polarization, and M-CSF receptor inhibition slows prostate cancer growth in model systems. As additional cytokines can direct TAM M2 polarization, targeting downstream transcription factors could avoid resistance. Klf4 and C/EBPβ each contribute to monocyte development, and reduced expression of macrophage Klf4 or C/EBPβ favors their adoption of a pro-inflammatory M1 state...
2018: PloS One
https://www.readbyqxmd.com/read/29323162/high-co-expression-of-il-34-and-m-csf-correlates-with-tumor-progression-and-poor-survival-in-lung-cancers
#10
Muhammad Baghdadi, Hiraku Endo, Atsushi Takano, Kozo Ishikawa, Yosuke Kameda, Haruka Wada, Yohei Miyagi, Tomoyuki Yokose, Hiroyuki Ito, Haruhiko Nakayama, Yataro Daigo, Nao Suzuki, Ken-Ichiro Seino
Despite recent advances in diagnosis and treatment of lung cancers, the 5-year survival rate remains unsatisfactory, which necessitates the identification of novel factors that associates with disease progression and malignant degree for improving diagnostic and therapeutic strategies. Recent progress in cancer immunology research has unveiled critical roles for colony stimulating factor 1 receptor (CSF1R) in multiple aspects of the tumor microenvironment. CSF1R is expressed on tumor-associated macrophages (TAMs), and mediates important pro-tumorigenic functions...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29299159/lactate-activated-macrophages-induced-aerobic-glycolysis-and-epithelial-mesenchymal-transition-in-breast-cancer-by-regulation-of-ccl5-ccr5-axis-a-positive-metabolic-feedback-loop
#11
Sensen Lin, Li Sun, Xiaodan Lyu, Xiongfei Ai, Danyu Du, Nan Su, Hongyang Li, Luyong Zhang, Jun Yu, Shengtao Yuan
Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296769/wnt-ligands-contribute-to-the-immune-response-during-septic-shock-and-amplify-endotoxemia-driven-inflammation-in-mice
#12
Marcela Gatica-Andrades, Dimitrios Vagenas, Jessica Kling, Tam T K Nguyen, Helen Benham, Ranjeny Thomas, Heinrich Körner, Bala Venkatesh, Jeremy Cohen, Antje Blumenthal
Improved understanding of the molecular mechanisms underlying dysregulated inflammatory responses in severe infection and septic shock is urgently needed to improve patient management and identify new therapeutic opportunities. The WNT signaling pathway has been implicated as a novel constituent of the immune response to infection, but its contribution to the host response in septic shock is unknown. Although individual WNT proteins have been ascribed pro- or anti-inflammatory functions, their concerted contributions to inflammation in vivo remain to be clearly defined...
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285315/cxcl8-derived-from-tumor-associated-macrophages-and-esophageal-squamous-cell-carcinomas-contributes-to-tumor-progression-by-promoting-migration-and-invasion-of-cancer-cells
#13
Masayoshi Hosono, Yu-Ichiro Koma, Nobuhisa Takase, Naoki Urakawa, Nobuhide Higashino, Kazuki Suemune, Himiko Kodaira, Mari Nishio, Manabu Shigeoka, Yoshihiro Kakeji, Hiroshi Yokozaki
Tumor-associated macrophages (TAMs) are involved in tumor progression and poor prognosis in several malignancies. We previously demonstrated the interaction between high numbers of infiltrating TAMs and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To investigate the significance of TAMs in ESCC, we conducted a cDNA microarray analysis of peripheral blood monocytes (PBMo)-derived macrophages and PBMo-derived macrophages stimulated with conditioned media of TE-series ESCC cell lines (TAM-like PBMo-derived macrophages)...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285224/soluble-chemokine-c-x-c-motif-ligand-16-cxcl16-in-urine-as-a-novel-biomarker-candidate-to-identify-high-grade-and-muscle-invasive-urothelial-carcinomas
#14
Kerstin Lang, Nadine Bonberg, Sibylle Robens, Thomas Behrens, Jan Hovanec, Thomas Deix, Katharina Braun, Florian Roghmann, Joachim Noldus, Volker Harth, Karl-Heinz Jöckel, Raimund Erbel, Yu Chun Tam, Andrea Tannapfel, Heiko Udo Käfferlein, Thomas Brüning
Information on biomarkers of urothelial carcinomas (UC) for clinical decision-making is limited. Here, we newly identified and verified CXCL16 as a promising novel biomarker in urine for high grade and muscle invasive UC in a cross-sectional cohort of 308 UC patients, 126 urological hospital controls, and 50 population controls using antibody arrays and ELISA. Median CXCL16 levels in urine was significantly higher in UC patients (273.2 pg/mg creatinine) compared to hospital (148.1 pg/mg) and population controls (85...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284682/glucocorticoids-induce-differentiation-of-monocytes-towards-macrophages-that-share-functional-and-phenotypical-aspects-with-erythroblastic-island-macrophages
#15
Esther Heideveld, Lea A Hampton-O'Neil, Stephen J Cross, Floris P J van Alphen, Maartje van den Biggelaar, Ashley M Toye, Emile van den Akker
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem cell survival. Here, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family...
December 28, 2017: Haematologica
https://www.readbyqxmd.com/read/29281816/tumor-associated-macrophages-derived-from-circulating-inflammatory-monocytes-degrade-collagen-through-cellular-uptake
#16
Daniel Hargbøl Madsen, Henrik Jessen Jürgensen, Majken Storm Siersbæk, Dorota Ewa Kuczek, Loretta Grey Cloud, Shihui Liu, Niels Behrendt, Lars Grøntved, Roberto Weigert, Thomas Henrik Bugge
Physiologic turnover of interstitial collagen is mediated by a sequential pathway in which collagen is fragmented by pericellular collagenases, endocytosed by collagen receptors, and routed to lysosomes for degradation by cathepsins. Here, we use intravital microscopy to investigate if malignant tumors, which are characterized by high rates of extracellular matrix turnover, utilize a similar collagen degradation pathway. Tumors of epithelial, mesenchymal, or neural crest origin all display vigorous endocytic collagen degradation...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29277763/the-expression-of-matrix-metalloproteinases-in-receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-expressing-cancer-of-apocrine-origin
#17
Yumi Kambayashi, Taku Fujimura, Sadanori Furudate, Chunbing Lyu, Takanori Hidaka, Aya Kakizaki, Yota Sato, Kayo Tanita, Setsuya Aiba
Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive tumor entity. Since there is no conventional therapy for advanced PCAC, exploratory treatments are sometimes used. As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). Since EMPD is a skin adenocarcinoma of apocrine gland origin that expresses high levels of RANKL and matrix metalloproteinase (MMP) 7, and EMPD is associated with the presence of RANK+ M2 macrophages, we hypothesized that tumor-associated macrophages (TAMs) in adenocarcinomas such as PCAC might also express RANKL and MMP7...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29274505/age-related-regulation-of-bone-formation-by-the-sympathetic-cannabinoid-cb1-receptor
#18
Saif Deis, Raj Kamal Srivastava, Inigo Ruiz de Azua, Laura Bindila, Saja Baraghithy, Beat Lutz, Itai Bab, Joseph Tam
The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves...
December 20, 2017: Bone
https://www.readbyqxmd.com/read/29274473/tyro3-mediated-phosphorylation-of-actn4-at-tyrosines-is-fak-dependent-and-decreases-susceptibility-to-cleavage-by-m-calpain
#19
Hanshuang Shao, Anna Wang, Douglas Lauffenburger, Alan Wells
Tyro3, a member of TAM receptor tyrosine kinase family, has been implicated in the regulation of melanoma progression and survival. In this study, we sought the molecular mechanism of Tyro3 effects avoiding endogenous background by overexpression of Tyro3 in fibroblasts that have negligible levels of Tyro3. This introduction triggers the tyrosyl-phosphorylation of ACTN4, a member of actin binding protein family involved in motility, a behavior critical for invasive progression, as shown by siRNA to Tyro3 limiting melanoma cell migration and invasion...
December 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29273600/deficiency-of-natriuretic-peptide-receptor-2-promotes-bicuspid-aortic-valves-aortic-valve-disease-left-ventricular-dysfunction-and-ascending-aortic-dilatations-in-mice
#20
Mark C Blaser, Kuiru Wei, Rachel L Adams, Yu-Qing Zhou, Laura-Lee Caruso, Zahra Mirzaei, Alan Lam, Richard K Tam, Hangjun Zhang, Scott P Heximer, Mark Henkelman, Craig A Simmons
Rationale: Aortic valve disease is a cell-mediated process without effective pharmacotherapy. C-type natriuretic peptide (CNP) inhibits myofibrogenesis and osteogenesis of cultured valve interstitial cells (VICs), and is downregulated in stenotic aortic valves. However, it is unknown whether CNP signaling regulates aortic valve health in vivo. Objective: To determine whether a deficient CNP signaling axis in mice causes accelerated progression of aortic valve disease. Methods and Results: In cultured porcine VICs, CNP inhibited pathological differentiation via the guanylate cyclase natriuretic peptide receptor 2 (NPR2) and not the G-protein-coupled clearance receptor NPR3...
December 22, 2017: Circulation Research
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