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macrophage and TAM

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https://www.readbyqxmd.com/read/29137420/anti-angiogenic-and-anti-tumor-effects-of-metronomic-use-of-novel-liposomal-zoledronic-acid-depletes-tumor-associated-macrophages-in-triple-negative-breast-cancer
#1
Xin-Jun Cai, Zeng Wang, Jia-Wei Cao, Jian-Jun Ni, Ying-Ying Xu, Jun Yao, Hong Xu, Fang Liu, Gao-Yi Yang
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth...
October 13, 2017: Oncotarget
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
#2
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
#3
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/29132376/ezh2-suppression-in-glioblastoma-shifts-microglia-toward-m1-phenotype-in-tumor-microenvironment
#4
Yatao Yin, Shuwei Qiu, Xiangpen Li, Bo Huang, Yun Xu, Ying Peng
BACKGROUND: Glioblastoma multiforme (GBM) induces tumor immunosuppression through interacting with tumor-infiltrating microglia or macrophages (TAMs) with an unclear pathogenesis. Enhancer of zeste homolog 2 (EZH2) is abundant in GBM samples and cell lines and is involved in GBM proliferation, cell cycle, and invasion, whereas its association with innate immune response is not yet reported. Herein, the aim of this study was to investigate the role of EZH2 in GBM immune. METHODS: Co-culturing models of human/murine GBM cells with PBMC-derived macrophages/primary microglia were employed...
November 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29129292/targeting-myeloid-cells-in-the-tumor-sustaining-microenvironment
#5
REVIEW
Jonathan Schupp, Franziska K Krebs, Niklas Zimmer, Emily Trzeciak, Detlef Schuppan, Andrea Tuettenberg
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29126881/triple-negative-breast-cancer-key-role-of-tumor-associated-macrophages-in-regulating-the-activity-of-anti-pd-1-pd-l1-agents
#6
REVIEW
Matteo Santoni, Emanuela Romagnoli, Tiziana Saladino, Laura Foghini, Stefania Guarino, Marco Capponi, Massimo Giannini, Paolo Decembrini Cognigni, Gerardo Ferrara, Nicola Battelli
Triple-negative breast cancer (TNBC) is associated with a poor prognosis, due to its aggressive behaviour and lack of effective targeted therapies. Immunocheckpoint inhibitors, such as anti-programmed cell death 1 (PD-1) and anti-PD-ligand(L)1 agents, are in course of investigation in TNBC, used alone or in combination with other systemic or local approaches. However, the high cost of these drugs and the lack of validated predictive biomarkers support the development of strategies aimed to overcome resistance and optimize the efficacy of these approaches...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29123259/tumour-infiltrating-inflammatory-and-immune-cells-in-patients-with-extrahepatic-cholangiocarcinoma
#7
Yuki Kitano, Hirohisa Okabe, Yo-Ichi Yamashita, Shigeki Nakagawa, Yoichi Saito, Naoki Umezaki, Masayo Tsukamoto, Takanobu Yamao, Kensuke Yamamura, Kota Arima, Takayoshi Kaida, Tatsunori Miyata, Kosuke Mima, Katsunori Imai, Daisuke Hashimoto, Yoshihiro Komohara, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba
BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated...
November 9, 2017: British Journal of Cancer
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/29111494/macrophages-as-a-potential-tumor-microenvironment-target-for-noninvasive-imaging-of-early-response-to-anticancer-therapy
#10
Qizhen Cao, Xinrui Yan, Kai Chen, Qian Huang, Marites P Melancon, Gabriel Lopez, Zhen Cheng, Chun Li
As a result of therapy-induced apoptosis, peripheral blood monocytes are recruited to tumors, where they become tumor-associated macrophages (TAMs). To date, few studies have investigated noninvasive molecular imaging for assessment of macrophage infiltration in response to therapy-induced apoptosis. Here, noninvasive assessment of changes in tumor accumulation of TAMs was proposed as a new way to measure early tumor response to anticancer therapy. Three different nanoparticles, QD710-Dendron quantum dots (QD710-D), Ferumoxytol, and PG-Gd-NIR813, were used for near-infrared fluorescence imaging, T2-weighted magnetic resonance imaging, and dual optical/T1-weighted MR imaging, respectively, in the MDA-MB-435 tumor model...
October 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/29111350/metabolic-changes-in-tumor-cells-and-tumor-associated-macrophages-a-mutual-relationship
#11
Romana T Netea-Maier, Johannes W A Smit, Mihai G Netea
In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs)...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29108252/circulating-exosomal-microrna-203-is-associated-with-metastasis-possibly-via-inducing-tumor-associated-macrophages-in-colorectal-cancer
#12
Yuki Takano, Takaaki Masuda, Hisae Iinuma, Rui Yamaguchi, Kuniaki Sato, Taro Tobo, Hidenari Hirata, Yosuke Kuroda, Sho Nambara, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Takahiro Ochiya, Katsuhiko Yanaga, Satoru Miyano, Koshi Mimori
A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203, a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106767/phagocyte-extracellular-matrix-crosstalk-empowers-tumour-development-and-dissemination
#13
REVIEW
Chen Varol, Irit Sagi
Phagocytes, such as tumour-associated macrophages (TAMs) and tumour-associated neutrophils (TANs), are abundant in the stroma of experimental and human tumours and are locally educated to mediate important biological functions that profoundly affect tumour initiation, growth and dissemination. Of considerable importance is the non- cellular component of the tumour microenvironment, namely - the extracellular matrix (ECM). This milieu is often overlooked due to its complexity and vast heterogeneity. Biophysical and biomechanical cues provided by the dynamically evolving tumourigenic ECM fundamentally modulate every behavioral facet of the cancer cells and of associated stromal cells...
November 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29097420/combination-of-cd40-agonism-and-csf-1r-blockade-reconditions-tumor-associated-macrophages-and-drives-potent-antitumor-immunity
#14
Karla R Wiehagen, Natasha M Girgis, Douglas H Yamada, Andressa A Smith, Szeman Ruby Chan, Iqbal S Grewal, Michael Quigley, Raluca I Verona
Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment (TME) to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen presenting cells (APCs) with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared to monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu...
November 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29095622/novel-trem-1-inhibitors-attenuate-tumor-growth-and-prolong-survival-in-experimental-pancreatic-cancer
#15
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/29095595/matrix-metalloproteinase-cleavable-nanoparticles-for-tumor-microenvironment-and-tumor-cell-dual-targeting-drug-delivery
#16
Zhenliang Sun, Ruihong Li, Ji Sun, You Peng, Linlin Xiao, Xingxing Zhang, Yixin Xu, Man Wang
Matrix metalloproteinases (MMPs), mostly abundant in the tumor extracellular matrix (ECM), tumor cells, and tumor vasculatures, are closely correlated with tumor progression and metastasis. In this case, making use of MMPs was supposed to achieve site-specific drug delivery and a satisfactory tumor treatment effect. Herein, we rationally developed a novel tumor microenvironment and tumor cell dual-targeting nanoparticle by integrating a chemotherapeutic-loaded drug-loaded carrier and a versatile polypeptide-LinTT1-PVGLIG-TAT (LPT) which is composed of a multitargeting peptide-LinTT1 and a cell-penetrating peptide-TAT...
November 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29090279/selenium-nanoparticles-induce-suppressed-function-of-tumor-associated-macrophages-and-inhibit-dalton-s-lymphoma-proliferation
#17
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
#18
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
#19
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/29077165/role-of-secreted-protein-acidic-in-hematogenous-metastasis-of-gastric-cancer
#20
A Mo, S-W Yang, Y-X Jiang, Y-L Zhao, Y Shi, F Qian, Y-X Hao, P-W Yu
OBJECTIVE: To investigate tumor microenvironment of metastasis (TMEM) and the expression of SPARC (secreted protein acidic and rich in cysteine) in gastric cancer, and their relationships with hematogenous metastasis. PATIENTS AND METHODS: Twenty-six pairs of cases with gastric cancer were enrolled, in which there were 26 cases with distant organ metastases and 26 cases of gastric cancer without organ metastases as controls. TMEM (by double-stained immunohistochemistry) and the expression of SPARC were determined in twenty-six pairs of cases...
October 2017: European Review for Medical and Pharmacological Sciences
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