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TAM receptors

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https://www.readbyqxmd.com/read/28073370/expression-site-of-p2ry12-in-residential-microglial-cells-in-astrocytomas-correlates-with-m1-and-m2-marker-expression-and-tumor-grade
#1
Changbin Zhu, Johan M Kros, Marcel van der Weiden, PingPin Zheng, Caroline Cheng, Dana A M Mustafa
The role of resident microglial cells in the pathogenesis and progression of glial tumors is still obscure mainly due to a lack of specific markers. Recently P2RY12, a P2 purinergic receptor, was introduced as a specific marker for microglial cells under normal and pathologic conditions. Here we analyzed the expression of P2RY12 in astrocytomas of various malignancy grades in relation to markers for M1 and M2 macrophage activation profiles by using two web-based glioma datasets and confocal immunohistochemistry to 28 astrocytoma samples grades II-IV...
January 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28063803/tamoxifen-and-ici-182-780-activate-hypothalamic-g-protein-coupled-estrogen-receptor-1-to-rapidly-facilitate-lordosis-in-female-rats
#2
Nathan Long, Bertha Long, Asma Mana, Dream Le, Lam Nguyen, Sima Chokr, Kevin Sinchak
In the female rat, sexual receptivity (lordosis) can be facilitated by sequential activation of estrogen receptor (ER) α and G protein-coupled estrogen receptor 1 (GPER) by estradiol. In the estradiol benzoate (EB) primed ovariectomized (OVX) rat, EB initially binds to ERα in the plasma membrane that complexes with and transactivates metabotropic glutamate receptor 1a to activate β-endorphin neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). This activates MPN μ-opioid receptors (MOP), inhibiting lordosis...
January 4, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28049839/gas6-is-a-key-homeostatic-immunological-regulator-of-host-commensal-interactions-in-the-oral-mucosa
#3
Maria Nassar, Yaara Tabib, Tal Capucha, Gabriel Mizraji, Tsipora Nir, Meirav Pevsner-Fischer, Gili Zilberman-Schapira, Oded Heyman, Gabriel Nussbaum, Herve Bercovier, Asaf Wilensky, Eran Elinav, Tal Burstyn-Cohen, Avi-Hai Hovav
The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand of the TYRO3-AXL-MERTK (TAM) receptor family, in regulating oral mucosal homeostasis. Expression of GAS6 was restricted to the outer layers of the oral epithelium...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28043912/ultrasound-mediated-destruction-of-oxygen-and-paclitaxel-loaded-dual-targeting-microbubbles-for-intraperitoneal-treatment-of-ovarian-cancer-xenografts
#4
Tingting Luo, Jiangchuan Sun, Shenyin Zhu, Juan He, Lan Hao, Linlin Xiao, Yi Zhu, Qianqian Wang, Xin Pan, Zhigang Wang, Shufang Chang
Folate receptor (FR) is overexpressed in many epithelial cancers and tumor-associated macrophages (TAMs), which enable it to function as an appropriate target for cancer treatment. We have successfully synthesized multifunctional folate-targeted and oxygen/paclitaxel loaded microbubbles (TOPLMBs) for ultrasound (US) mediated delivery for combination therapy in an intraperitoneal ovarian cancer xenograft model. The TOPLMBs target both ovarian cancer cells and TAMs and provide a promising drug delivery strategy for the combination treatment of ovarian cancer and tumor microenvironment...
December 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28039457/tumor-associated-macrophages-promote-prostate-cancer-migration-through-activation-of-the-ccl22-ccr4-axis
#5
Aerken Maolake, Kouji Izumi, Kazuyoshi Shigehara, Ariunbold Natsagdorj, Hiroaki Iwamoto, Suguru Kadomoto, Yuta Takezawa, Kazuaki Machioka, Kazutaka Narimoto, Mikio Namiki, Wen-Jye Lin, Guzailinuer Wufuer, Atsushi Mizokami
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038451/androgen-receptor-transcriptionally-regulates-semaphorin-3c-in-a-gata2-dependent-manner
#6
Kevin J Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Shahram Khosravi, Parvin Yenki, Charan Tse, James W Peacock, Aishwariya Sharma, Yan Ting Chiang, Yuzhuo Wang, Artem Cherkasov, Paul S Rennie, Martin E Gleave, Christopher J Ong
The androgen receptor (AR) is a member of the nuclear receptor superfamily of transcription factors and is central to prostate cancer (PCa) progression. Ligand-activated AR engages androgen response elements (AREs) at androgen-responsive genes to drive the expression of gene batteries involved in cell proliferation and cell fate. Understanding the transcriptional targets of the AR has become critical in apprehending the mechanisms driving treatment-resistant stages of PCa. Although AR transcription regulation has been extensively studied, the signaling networks downstream of AR are incompletely described...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035396/anticancer-effect-of-luteolin-is-mediated-by-downregulation-of-tam-receptor-tyrosine-kinases-but-not-interleukin-8-in-non-small-cell-lung-cancer-cells
#7
Youn Ju Lee, Taeho Lim, Min Su Han, Sun-Hwa Lee, Suk-Hwan Baek, Hong-Yan Nan, Chuhee Lee
TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells...
December 23, 2016: Oncology Reports
https://www.readbyqxmd.com/read/28034848/regulated-intramembrane-proteolysis-of-the-axl-receptor-kinase-generates-an-intracellular-domain-that-localizes-in-the-nucleus-of-cancer-cells
#8
Yinzhong Lu, Jun Wan, Zhifeng Yang, Xiling Lei, Qi Niu, Lanxin Jiang, Willemijn M Passtoors, Aiping Zang, Patrick C Fraering, Fang Wu
Deregulation of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases (RTKs) has recently been demonstrated to predominately promote survival and chemoresistance of cancer cells. Intramembrane proteolysis mediated by presenilin/γ-secretase is known to regulate the homeostasis of some RTKs. In the present study, we demonstrate that AXL, but not TYRO3 or MERTK, is efficiently and sequentially cleaved by α- and γ-secretases in various types of cancer cell lines. Proteolytic processing of AXL redirected signaling toward a secretase-mediated pathway, away from the classic, well-known, ligand-dependent canonical RTK signaling pathway...
December 29, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28031265/the-carbohydrate-lectin-receptor-dectin-1-mediates-immune-response-to-exserohilum-rostratum
#9
Jennifer L Reedy, Paige E Negoro, Marianela Feliu, Allison K Lord, Nida S Khan, Dan P Lukason, Nathan P Wiederhold, Jenny M Tam, Michael K Mansour, Thomas F Patterson, Jatin M Vyas
Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease including infections associated with high rates of mortality. Despite this, the mechanism of innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 751 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum Despite lack of phagocytosis, macrophage production of TNFα is triggered by hyphae, but not spores, and depends upon Dectin-1, a C-type lectin receptor...
December 28, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27993670/interactome-of-the-inhibitory-isoform-of-the-nuclear-transporter-importin-13
#10
Shadma Fatima, Kylie M Wagstaff, Kim G Lieu, Rebecca G Davies, Satomi S Tanaka, Yasuka L Yamaguchi, Kate L Loveland, Patrick P L Tam, David A Jans
Importin 13 (Imp13) is a bidirectional nuclear transporter of proteins involved in a range of important cellular processes, with an N-terminally truncated inhibitory isoform (tImp13) specifically expressed in testis. To gain insight into tImp13 function, we performed a yeast-2-hybrid screen from a human testis cDNA library, identifying for the first time a suite of interactors with roles in diverse cellular process. We validated the interaction of tImp13 with Eukaryotic translation initiation factor 4γ2 (EIF4G2) and High mobility group containing protein 20A (HMG20A), benchmarking that with glucocorticoid receptor (GR), a known Imp13 interactor expressed in testis...
December 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27977181/an-orally-active-bradykinin-b1-receptor-antagonist-engineered-as-a-bifunctional-chimera-of-sunflower-trypsin-inhibitor
#11
Yibo Qiu, Misako Taichi, Na Wei, Huan Yang, Kathy Qian Luo, James P Tam
An orally active and metabolically stable peptide TIBA was successfully engineered as a chimera by fusing an analgesic bradykinin receptor antagonist peptide and the trypsin inhibitory loop of sunflower trypsin inhibitor-1. As a fusion cyclic peptide, the metabolically labile analgesic peptide is protected from degradation by exopeptidases as well as the endopeptidases, and its serum half-life extended from <5 min to >6 h as a chimera. Moreover, the chimera TIBA was also found to be orally active in an animal pain model using a hot plate assay...
December 15, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27965453/staphylococcus-aureus-leukocidin-luked-and-hiv-1-gp120-target-different-sequence-determinants-on-ccr5
#12
Kayan Tam, Megan Schultz, Tamara Reyes-Robles, Bénédicte Vanwalscappel, Joshua Horton, Francis Alonzo, Beili Wu, Nathaniel R Landau, Victor J Torres
: Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27958361/deficiency-of-axl-in-bone-marrow-derived-cells-does-not-affect-advanced-atherosclerotic-lesion-progression
#13
Manikandan Subramanian, Jonathan D Proto, Glenn K Matsushima, Ira Tabas
AXL, a member of the TAM (Tyro3, Axl, MerTK) family of receptors, plays important roles in cell survival, clearance of dead cells (efferocytosis), and suppression of inflammation, which are processes that critically influence atherosclerosis progression. Whereas MerTK deficiency promotes defective efferocytosis, inflammation, and plaque necrosis in advanced murine atherosclerosis, the role of Axl in advanced atherosclerosis progression is not known. Towards this end, bone marrow cells from Axl(-/-) or wild-type mice were transplanted into lethally irradiated Ldlr(-/-) mice...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936172/tamoxifen-isomers-and-metabolites-exhibit-distinct-affinity-and-activity-at-cannabinoid-receptors-potential-scaffold-for-drug-development
#14
Benjamin M Ford, Lirit N Franks, Anna Radominska-Pandya, Paul L Prather
Tamoxifen (Tam) is a selective estrogen receptor (ER) modulator (SERM) that is an essential drug to treat ER-positive breast cancer. Aside from known actions at ERs, recent studies have suggested that some SERMs like Tam also exhibit novel activity at cannabinoid subtype 1 and 2 receptors (CB1R and CB2Rs). Interestingly, cis- (E-Tam) and trans- (Z-Tam) isomers of Tam exhibit over a 100-fold difference in affinity for ERs. Therefore, the current study assessed individual isomers of Tam and subsequent cytochrome P450 metabolic products, 4-hydroxytamoxifen (4OHT) and 4-hydroxy-N-desmethyl tamoxifen (End) for affinity and activity at CBRs...
2016: PloS One
https://www.readbyqxmd.com/read/27916840/ligand-activation-of-tam-family-receptors-implications-for-tumor-biology-and-therapeutic-response
#15
REVIEW
Viralkumar Davra, Stanley G Kimani, David Calianese, Raymond B Birge
The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology...
November 29, 2016: Cancers
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#16
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27900261/targeting-the-endocannabinoid-cb1-receptor-system-for-treating-obesity-in-prader-willi-syndrome
#17
Ibrahim Knani, Brian J Earley, Shiran Udi, Alina Nemirovski, Rivka Hadar, Asaad Gammal, Resat Cinar, Harry J Hirsch, Yehuda Pollak, Itai Gross, Talia Eldar-Geva, Daniela P Reyes-Capo, Joan C Han, Andrea M Haqq, Varda Gross-Tsur, Rachel Wevrick, Joseph Tam
OBJECTIVE: Extreme obesity is a core phenotypic feature of Prader-Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#18
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27889048/the-use-of-high-dose-estrogens-for-the-treatment-of-breast-cancer
#19
REVIEW
Herjan J T Coelingh Bennink, Carole Verhoeven, Alice E Dutman, Jos Thijssen
Estrogens are known to stimulate the growth of breast cancer but they are also an effective treatment for this disease (this has been termed the 'estrogen paradox'). The fact that estrogens can be an effective treatment for breast cancer is something that has almost been forgotten, whereas the fear for estrogens remains. This paper reviews the use of estrogens for the treatment of breast cancer and identifies possible applications. The data summarised in this review demonstrate that high-dose estrogens are effective for the treatment of advanced breast cancer, both as first-line treatment as well as for treatment after occurrence of endocrine resistance to TAM and AIs...
January 2017: Maturitas
https://www.readbyqxmd.com/read/27883134/non-fluorescent-quantification-of-single-mrna-with-transient-absorption-microscopy
#20
Jing Liu, Joseph M K Irudayaraj
Single molecule detection is confounded by the background signals from the biological environment, such as autofluorescence, Rayleigh scattering, or turbidity in cells and tissues. In this article, we report on the utilization of gold nanoparticles (AuNPs) as an orthogonal probe for non-fluorescence detection of single molecules with a transient absorption microscopy (TAM). The developed system and concepts were validated by quantitative evaluation of human epidermal receptor 2 (Her2) mRNA in cancer cells and tissues at single copy sensitivity...
November 24, 2016: Nanoscale
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