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https://www.readbyqxmd.com/read/29148078/soluble-tam-receptor-tyrosine-kinases-in-rheumatoid-arthritis-correlation-with-disease-activity-and-bone-destruction
#1
Liling Xu, Fanlei Hu, Huaqun Zhu, Xu Liu, Lianjie Shi, Yun Li, Hua Zhong, Su Yin
The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well-explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in the patients with RA. 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled in this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by ELISA, then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analyzed...
November 17, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29142426/in-silico-and-in-vitro-anticancer-activity-of-isolated-novel-marker-compound-from-chemically-modified-bioactive-fraction-from-curcuma-longa-nccl
#2
Arshi Naqvi, Richa Malasoni, Swati Gupta, Akansha Srivastava, Rishi R Pandey, Anil Kumar Dwivedi
Background: Turmeric (Curcuma longa) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. Objective: In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). Materials and Methods: NCCL was prepared from HM...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142311/a-standardized-herbal-extract-mitigates-tumor-inflammation-and-augments-chemotherapy-effect-of-docetaxel-in-prostate-cancer
#3
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Yu-Chih Yang, Yi-Wen Hsiao, Mong-Hsun Tsai, Pei-Wen Hsiao
Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138497/rapid-purification-of-human-bispecific-antibodies-via-selective-modulation-of-protein-a-binding
#4
Adam Zwolak, Catherine N Leettola, Susan H Tam, Dennis R Goulet, Mehabaw G Derebe, Jose R Pardinas, Songmao Zheng, Rose Decker, Eva Emmell, Mark L Chiu
Methods to rapidly generate high quality bispecific antibodies (BsAb) having normal half-lives are critical for therapeutic programs. Here, we identify 3 mutations (T307P, L309Q, and Q311R or "TLQ") in the Fc region of human IgG1 which disrupt interaction with protein A while enhancing interaction with FcRn. The mutations are shown to incrementally alter the pH at which a mAb elutes from protein A affinity resin. A BsAb comprised of a TLQ mutant and a wild-type IgG1 can be efficiently separated from contaminating parental mAbs by differential protein A elution starting from either a) purified parental mAbs, b) in-supernatant crossed parental mAbs, or c) co-transfected mAbs...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29136508/cancer-associated-fibroblasts-neutralize-the-anti-tumor-effect-of-csf1-receptor-blockade-by-inducing-pmn-mdsc-infiltration-of-tumors
#5
Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W Speicher, Ashani T Weeraratna, Timothy Chao, Robert H Vonderheide, Lucia R Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A Sepulveda, Linda A Snyder, Dmitry I Gabrilovich
Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29133618/therapeutic-impact-of-nanoparticle-therapy-targeting-tumor-associate-macrophages
#6
Courtney Penn, Kun Yang, Hong Zong, Jae-Young Lim, Alex Cole, Dongli Yang, James Baker, Sascha N Goonewardena, Ronald J Buckanovich
Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest anti-angiogenic therapy induced hypoxia can induce tumor "stemness' as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor associated macrophages (TAMs). As such TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29131988/treatment-adoption-and-relative-effectiveness-of-aromatase-inhibitors-compared-to-tamoxifen-in-early-breast-cancer-a-multi-institutional-observational-study
#7
Arlindo R Ferreira, Ana Palha, Lurdes Correia, Pedro Filipe, Vasco Rodrigues, Ana Miranda, Rosário André, João Fernandes, Joaquim Gouveia, José L Passos-Coelho, António Moreira, Margarida Brito, Joana Ribeiro, Otto Metzger-Filho, Nancy U Lin, Luís Costa, Inês Vaz-Luis
BACKGROUND: Since 2005, aromatase inhibitors (AIs) have been the adjuvant treatment of choice for postmenopausal women with early breast cancer (BC). In this study we characterize the adoption of AIs in Portugal, variables associated with treatment administration, and compare its effectiveness (either in monotherapy or sequential therapy) to tamoxifen monotherapy (TAM). PATIENTS AND METHODS: This was a retrospective cohort study that included postmenopausal women with stage I-III hormone receptor (HR) positive BC diagnosed from 2006 to 2008 and treated with adjuvant endocrine therapy in four participating institutions...
November 10, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29116108/precision-targeting-of-tumor-macrophages-with-a-cd206-binding-peptide
#8
Pablo Scodeller, Lorena Simón-Gracia, Sergei Kopanchuk, Allan Tobi, Kalle Kilk, Pille Säälik, Kaarel Kurm, Mario Leonardo Squadrito, Venkata Ramana Kotamraju, Ago Rinken, Michele De Palma, Erkki Ruoslahti, Tambet Teesalu
Tumor-associated macrophages (TAMs) expressing the multi-ligand endocytic receptor mannose receptor (CD206/MRC1) contribute to tumor immunosuppression, angiogenesis, metastasis, and relapse. Here, we describe a peptide that selectively targets MRC1-expressing TAMs (MEMs). We performed in vivo peptide phage display screens in mice bearing 4T1 metastatic breast tumors to identify peptides that target peritoneal macrophages. Deep sequencing of the peptide-encoding inserts in the selected phage pool revealed enrichment of the peptide CSPGAKVRC (codenamed "UNO")...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113264/cancer-cell-expressed-b7-h3-regulates-the-differentiation-of-tumor-associated-macrophages-in-human-colorectal-carcinoma
#9
Yong Mao, Lujun Chen, Fengming Wang, Dawei Zhu, Xiaosong Ge, Dong Hua, Jing Sun
Co-stimulatory molecule B7 homolog 3 protein (B7-H3) has been described as an important tumor antigen in various human tumors. The exact role of B7-H3 in tumor progression and its receptor are still ambiguous. The phenotype and the function of tumor-associated macrophages (TAMs) in human solid tumors are complicated and could contribute to the shaping of the tumor microenvironment. In the present study, B7-H3 expression and lymphocyte infiltration were investigated by immunohistochemistry in 117 colorectal carcinoma (CRC) patients...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100386/hypomethylation-associated-enhanced-transcription-of-trefoil-factor-3-mediates-tamoxifen-stimulated-oncogenicity-of-er-endometrial-carcinoma-cells
#10
Vijay Pandey, Min Zhang, Qing-Yun Chong, Mingliang You, Ainiah Rushdiana Raquib, Amit K Pandey, Dong-Xu Liu, Liang Liu, Lan Ma, Sudhakar Jha, Zheng-Sheng Wu, Tao Zhu, Peter E Lobie
Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 (TFF3), in oestrogen receptor-positive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098396/survival-benefit-of-tamoxifen-and-aromatase-inhibitor-in-male-and-female-breast-cancer
#11
Holm Eggemann, Udo Altmann, Serban-Dan Costa, Atanas Ignatov
BACKGROUND: Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). PATIENTS AND METHODS: We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. RESULTS: The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated...
November 2, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29095622/novel-trem-1-inhibitors-attenuate-tumor-growth-and-prolong-survival-in-experimental-pancreatic-cancer
#12
Zu T Shen, Alexander B Sigalov
Pancreatic cancer (PC) is a highly lethal cancer with an urgent need to expand the limited treatment options for patients. Tumor-associated macrophages (TAMs) promote tumor aggressiveness and metastasis. High expression of triggering receptor expressed on myeloid cells 1 (TREM-1) on TAMs directly correlates with poor survival in patients with non-small cell lung cancer (NSCLC). We have previously hypothesized that blockade of TREM-1 could be a promising therapeutic strategy to treat cancer and shown that the novel, ligand-independent TREM-1 inhibitory peptides rationally designed using the signaling chain homooligomerization (SCHOOL) strategy suppress NSCLC growth in vivo...
November 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29091270/a-high-throughput-method-to-study-the-physiology-of-e2-er%C3%AE-signaling-in-breast-cancer-cells
#13
Stefano Leone, Claudia Busonero, Filippo Acconcia
17β-estradiol (E2) regulates diverse physiological effects including cell proliferation through the estrogen receptor α (ERα), which as a transcription factor drives gene transcription and as an extra-nuclear localized receptor triggers the membrane-dependent activation of diverse kinase cascades. E2 also modifies ERα intracellular levels via diverse intracellular mechanisms. In this way, the E2-acivated ERα integrates signaling cascades with the modulation of receptor intracellular concentration and with the induction of DNA synthesis and ultimately drives cell proliferation...
November 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29090279/selenium-nanoparticles-induce-suppressed-function-of-tumor-associated-macrophages-and-inhibit-dalton-s-lymphoma-proliferation
#14
Pramod Kumar Gautam, Sanjay Kumar, M S Tomar, Rishi Kant Singh, A Acharya, Sanjay Kumar, B Ram
Selenium Nanoparticle (SeNPs) is reported that it enhances and maintains optimal immune during infection and malignancies. To this end, we examined the role of selenium on TAMS whose anti-tumor function suppressed which favor tumor progression. BALB/c (H2d) strain of mice non-Hodgkin type of Dalton's cell line was used to check the role of carboxlic group induced, synthesized SeNPs on TAMs. Screening of IC50 value was done primarily trypen blue exclusion assay and 50% proliferation of DL cells inhibited 40 ng/ml to 50 ng/...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29084248/tti-621-sirp%C3%AE-fc-a-cd47-blocking-cancer-immunotherapeutic-triggers-phagocytosis-of-lymphoma-cells-by-multiple-polarized-macrophage-subsets
#15
Gloria H Y Lin, Vien Chai, Vivian Lee, Karen Dodge, Tran Truong, Mark Wong, Lisa D Johnson, Emma Linderoth, Xinli Pang, Jeff Winston, Penka S Petrova, Robert A Uger, Natasja N Viller
Tumor-associated macrophages (TAMs) are heterogeneous and can adopt a spectrum of activation states between pro-inflammatory and pro-tumorigenic in response to the microenvironment. We have previously shown that TTI-621, a soluble SIRPαFc fusion protein that blocks the CD47 "do-not-eat" signal, promotes tumor cell phagocytosis by IFN-γ-primed macrophages. To assess the impact of CD47 blockade on diverse types of macrophages that are found within the tumor microenvironment, six different polarized human macrophage subsets (M(-), M(IFN-γ), M(IFN-γ+LPS), M(IL-4), M(HAGG+IL-1β), M(IL-10 + TGFβ)) with distinct cell surface markers and cytokine profiles were generated...
2017: PloS One
https://www.readbyqxmd.com/read/29079064/wandering-pathways-in-the-regulation-of-innate-immunity-and-inflammation
#16
REVIEW
Alberto Mantovani
Tumor-associated macrophages (TAM) have served as a paradigm of cancer-related inflammation. Moreover, investigations on TAM have led to the dissection of macrophage plasticity and polarization and to the discovery and analysis of molecular pathways of innate immunity, in particular cytokines, chemokines and PTX3 as a prototypic fluid phase pattern recognition molecule. Mechanisms of negative regulation are complex and include decoy receptors, receptor antagonists, anti-inflammatory cytokines and the signalling regulator IL-1R8...
October 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29071196/trail-functionalized-gold-nanoparticles-selectively-trigger-apoptosis-in-polarized-macrophages
#17
Yen-Jang Huang, Shan-Hui Hsu
Tumor-associated macrophages (TAMs) have the same immunosuppressive effects as M2 macrophages in tumor progression and are correlated with poor-patient prognosis and survival in non-small cell lung cancer (NSCLC). Therefore, TAMs are the potential targets for cancer therapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of tumor necrosis factor superfamily and selectively induces cancer cell apoptosis, but not in most normal cells. Nanoparticles coated with multiple ligands can act as multivalent ligands that may actively crosslink cell surface receptors to affect downstream signals...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29066614/targeting-the-stat6-pathway-in-tumor-associated-macrophages-reduces-tumor-growth-and-metastatic-niche-formation-in-breast-cancer
#18
Karin Binnemars-Postma, Ruchi Bansal, Gert Storm, Jai Prakash
Tumor-associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. These protumoral macrophages display an M2 phenotype induced by IL-4 and IL-13 cytokines. In this study, we hypothesized that the inhibition of the signal transducer and activator of transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL-4 and IL-13, may be an interesting strategy by which to inhibit TAM differentiation and, thus, their protumorigenic activities...
October 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29062042/contributions-of-myd88-dependent-receptors-and-cd11c-positive-cells-to-corneal-epithelial-barrier-function-against-pseudomonas-aeruginosa
#19
Matteo M E Metruccio, Connie Tam, David J Evans, Anna L Xie, Michael E Stern, Suzanne M J Fleiszig
Previously we reported that corneal epithelial barrier function against Pseudomonas aeruginosa was MyD88-dependent. Here, we explored contributions of MyD88-dependent receptors using vital mouse eyes and confocal imaging. Uninjured IL-1R (-/-) or TLR4 (-/-) corneas, but not TLR2 (-/-), TLR5 (-/-), TLR7 (-/-), or TLR9 (-/-), were more susceptible to P. aeruginosa adhesion than wild-type (3.8-fold, 3.6-fold respectively). Bacteria adherent to the corneas of IL-1R (-/-) or TLR5 (-/-) mice penetrated beyond the epithelial surface only if the cornea was superficially-injured...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29059867/spatial-targeting-of-tumor-associated-macrophage-and-tumor-cells-with-a-designer-nanocarrier-for-cancer-chemo-immunotherapy
#20
Jun Wang
form only given. Chemo-immunotherapy which combines chemotherapeutics with immune-modulating agents represents an appealing approach to improving cancer therapy [1, 2]. To maximize its efficacy, differential and precise targeting of the multiple therapeutics into corresponding cells is desirable. Here we develop an immunostimulatory nanocarrier that simultaneously loads platinum (Pt)-based chemotherapeutic prodrug and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of tumor-associated macrophages (TAMs) [3], to spatially target tumor cells and TAMs for cancer chemo-immunotherapy...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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