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https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#1
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28209156/breastdefend-enhances-effect-of-tamoxifen-in-estrogen-receptor-positive-human-breast-cancer-in-vitro-and-in-vivo
#2
Shujie Cheng, Victor Castillo, Matt Welty, Mark Alvarado, Isaac Eliaz, Constance J Temm, George E Sandusky, Daniel Sliva
BACKGROUND: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. METHODS: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively...
February 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28202524/scavenger-receptor-a1-prevents-metastasis-of-non-small-cell-lung-cancer-via-suppression-of-macrophage-serum-amyloid-a1
#3
Yan Zhang, Yongyue Wei, Bin Jiang, Lili Chen, Hui Bai, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, David C Christiani, Qi Chen
Mechanisms of crosstalk between tumor cells and tumor-associated macrophages (TAM) which drive metastasis are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced-stage NSCLC patients in the Harvard Lung Cancer Study cohort...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28192441/cyclic-amp-regulates-postnatal-development-of-neural-and-behavioral-responses-to-nacl-in-rats
#4
Jie Qian, Shobha Mummalaneni, Tam-Hao T Phan, Gerard L Heck, John A DeSimone, David West, Sunila Mahavadi, Deanna Hojati, Karnam S Murthy, Mee-Ra Rhyu, Andrew I Spielman, Mehmet Hakan Özdener, Vijay Lyall
During postnatal development rats demonstrate an age-dependent increase in NaCl chorda tympani (CT) responses and the number of functional apical amiloride-sensitive epithelial Na+ channels (ENaCs) in salt sensing fungiform (FF) taste receptor cells (TRCs). Currently, the intracellular signals that regulate the postnatal development of salt taste have not been identified. We investigated the effect of cAMP, a downstream signal for arginine vasopressin (AVP) action, on the postnatal development of NaCl responses in 19-23 day old rats...
2017: PloS One
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#5
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28185790/immune-regulation-of-antibody-access-to-neuronal-tissues
#6
REVIEW
Akiko Iwasaki
This review highlights recent advances in how the innate and adaptive immune systems control the blood-brain barrier (BBB) and the blood-nerve barrier (BNB). Interferons and TAM receptors play key roles in innate immune control of the BBB. Cells of the adaptive immune system, particularly CD4(+) T cells, take distinct routes to enter neural tissues and mediate immune surveillance. Furthermore, T cell-mediated opening of the BBB and the BNB is crucial to allow antibody access and thereby block the replication of neurotropic viruses...
February 6, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#7
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
: Tyro3, Axl and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28176769/heterogeneity-of-macrophage-infiltration-and-therapeutic-response-in-lung-carcinoma-revealed-by-3d-organ-imaging
#8
Michael F Cuccarese, J Matthew Dubach, Christina Pfirschke, Camilla Engblom, Christopher Garris, Miles A Miller, Mikael J Pittet, Ralph Weissleder
Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28166815/regulation-of-submaxillary-gland-androgen-regulated-protein-3a-via-estrogen-receptor-2-in-radioresistant-head-and-neck-squamous-cell-carcinoma-cells
#9
Jennifer Grünow, Chao Rong, Jan Hischmann, Karim Zaoui, Christa Flechtenmacher, Klaus-Josef Weber, Peter Plinkert, Jochen Hess
BACKGROUND: Molecular mechanisms of intrinsic or acquired radioresistance serve as critical barrier for curative therapy of head and neck squamous cell carcinoma (HNSCC) and remain a major obstacle for progression-free and disease-specific survival. METHODS: HNSCC cell lines were treated with a protocol of fractionated irradiation (IR, 4× 2Gy) alone or in combination with antagonists of estrogen receptor signaling and viability was determined by a colony-forming assay (CFA)...
February 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28154173/autocrine-and-paracrine-interactions-between-multiple-myeloma-cells-and-bone-marrow-stromal-cells-by-growth-arrest-specific-gene-6-crosstalk-with-interleukin-6
#10
Miki Furukawa, Hiroshi Ohkawara, Kazuei Ogawa, Kazuhiko Ikeda, Koki Ueda, Akiko Shichishima-Nakamura, Emi Ito, Jun-Ichi Imai, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Satoshi Waguri, Takayuki Ikezoe, Yasuchika Takeishi
The pathogenesis of multiple myeloma (MM) has not yet been fully elucidated. Our microarray analysis and immunohistochemistry revealed significant upregulation of growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein with a structural homology with protein S, in bone marrow (BM) cells of MM patients. ELISA showed that the serum levels of soluble Gas6 were significantly increased in the MM patients when compared with healthy controls. Gas6 was overexpressed in the human CD138-positive MM cell line RPMI-8226...
January 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28152498/extended-adjuvant-endocrine-therapy-a-standard-to-all-or-some
#11
REVIEW
Domen Ribnikar, Berta Sousa, Tanja Cufer, Fatima Cardoso
Patients with estrogen receptor-positive (ER +) early breast cancer (EBC) are at a continuous risk for distant relapse despite 5 years of standard endocrine therapy, even after 10-15 years after primary diagnosis. Hence, large randomized clinical trials were conducted to evaluate the role of extended endocrine treatment (ET) with the primary goal to prevent or at least delay distant relapse. Two very large trials of extended tamoxifen (TAM), the ATLAS and the aTTom trial, proved the efficacy of prolonged TAM particularly important after 10 years due to the carry-over effect of the five initial years...
January 30, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28145605/the-tam-receptor-tyro3-regulates-myelination-in-the-central-nervous-system
#12
Rainer Akkermann, Andrea Aprico, Ashwyn A Perera, Helena Bujalka, Alistair E Cole, Junhua Xiao, Judith Field, Trevor J Kilpatrick, Michele D Binder
Myelin is an essential component of the mammalian nervous system, facilitating rapid conduction of electrical impulses by axons, as well as providing trophic support to neurons. Within the central nervous system, the oligodendrocyte is the specialized neural cell responsible for producing myelin by a process that is thought to be regulated by both activity dependent and independent mechanisms but in incompletely understood ways. We have previously identified that the protein Gas6, a ligand for a family of tyrosine kinase receptors known as the TAM (Tyro3, Axl, and Mertk) receptors, directly increases oligodendrocyte induced myelination in vitro...
February 1, 2017: Glia
https://www.readbyqxmd.com/read/28145500/muscle-specific-overexpression-of-adipor1-or-adipor2-gives-rise-to-common-and-discrete-local-effects-whilst-adipor2-promotes-additional-systemic-effects
#13
Sahar Keshvari, Darren C Henstridge, Choaping Ng, Mark A Febbraio, Jonathan P Whitehead
Hypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 ((TAM)R1) or AdipoR2 ((TAM)R2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#14
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28118606/protein-s-drives-oral-squamous-cell-carcinoma-tumorigenicity-through-regulation-of-axl
#15
Ghada Abboud-Jarrous, Shivam Priya, Avi Maimon, Stuart Fischman, Mayan Cohen-Elisha, Rakefet Czerninski, Tal Burstyn-Cohen
The TAM family of proto-oncogenic receptor protein tyrosine kinases, comprising of TYRO3, AXL, and MERTK, is implicated in many human cancers. Their activation leads to cancer cell proliferation, enhanced migration, invasion, and drug resistance; however how TAMs are activated in cancers is less understood. We previously showed that Protein S (PROS1) is a ligand of the TAM receptors. Here we identify PROS1 as a mediator of Oral Squamous Cell Carcinoma (OSCC) in proliferation, cell survival and migration. We demonstrate that excess PROS1 induces OSCC proliferation and migration...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28111081/phosphatidylserine-exposure-controls-viral-innate-immune-responses-by-microglia
#16
Yusuf Tufail, Daniela Cook, Lawrence Fourgeaud, Colin J Powers, Katharina Merten, Charles L Clark, Elizabeth Hoffman, Alexander Ngo, Kohei J Sekiguchi, Clodagh C O'Shea, Greg Lemke, Axel Nimmerjahn
Microglia are the intrinsic immune sentinels of the central nervous system. Their activation restricts tissue injury and pathogen spread, but in some settings, including viral infection, this response can contribute to cell death and disease. Identifying mechanisms that control microglial responses is therefore an important objective. Using replication-incompetent adenovirus 5 (Ad5)-based vectors as a model, we investigated the mechanisms through which microglia recognize and respond to viral uptake. Transgenic, immunohistochemical, molecular-genetic, and fluorescence imaging approaches revealed that phosphatidylserine (PtdSer) exposure on the outer leaflet of transduced cells triggers their engulfment by microglia through TAM receptor-dependent mechanisms...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28098359/m2-like-macrophages-induce-colon-cancer-cell-invasion-via-matrix-metalloproteinases
#17
Katyayni Vinnakota, Yuan Zhang, Benson Chellakkan Selvanesan, Geriolda Topi, Tavga Salim, Janna Sand-Dejmek, Gunilla Jönsson, Anita Sjölander
The inflammatory milieu plays an important role in colon cancer development and progression. Previously, we have shown that tumor-associated macrophages (TAMs), an important component of the tumor microenvironment, are enriched in tumors compared with normal tissue and confer a poorer prognosis. In the present study, we found that matrix metallopeptidase-9 (MMP-9), which degrades extracellular matrix proteins, was increased in biopsies from colon cancer patients and in mouse xenografts with SW480 cell-derived tumors...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28096479/igf-1-receptor-modulates-foxo1-mediated-tamoxifen-response-in-breast-cancer-cells
#18
Ali Vaziri-Gohar, Yan Zheng, Kevin D Houston
: Tamoxifen is a common adjuvant treatment for ERalpha-positive breast cancer patients, however acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein-coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor binding protein-1 (IGFBP-1) to inhibit IGF-1-dependent signaling. To determine if dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment...
January 17, 2017: Molecular Cancer Research: MCR
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
#19
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
#20
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
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