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macrophage and TAM

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https://www.readbyqxmd.com/read/28638736/transcriptional-factor-eb-regulates-macrophage-polarization-in-the-tumor-microenvironment
#1
Liang Fang, Johnie Hodge, Fatma Saaoud, Junfeng Wang, Stephen Iwanowycz, Yuzhen Wang, Yvonne Hui, Trent D Evans, Babak Razani, Daping Fan
Tumor microenvironment (TME) contains a variety of infiltrating immune cells. Among them, tumor-associated macrophages (TAMs) and their alternative activation contribute greatly to the progression of tumors. The mechanisms governing macrophage polarization in the TME are unclear. Here, we show that in TAMs or macrophages under tumor-conditioned medium treatment, the expression of transcription factor EB (TFEB) is reduced and more of the TFEB protein is in an inactive cytosolic form. Transforming growth factor (TGF)-β is identified as a main driving force for the reduced TFEB expression and activity in TAMs via activating ERK signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#2
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633143/tumor-associated-macrophages-in-the-development-of-4-nitroquinoline-1-oxide-induced-tongue-squamous-cell-carcinoma-in-a-mouse-model
#3
Kentaro Miki, Yorihisa Orita, Yuka Gion, Soshi Takao, Kyotaro Ohno, Mai Takeuchi, Toshihiro Ito, Akira Minoura, Tomoyasu Tachibana, Hidenori Marunaka, Takuma Makino, Akihiro Matsukawa, Kazunori Nishizaki, Tadashi Yoshino, Yasuharu Sato
OBJECTIVE: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. METHODS: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed...
June 21, 2017: Oncology
https://www.readbyqxmd.com/read/28630636/targeting-tumor-microenvironment-effects-of-chinese-herbal-formulae-on-macrophage-mediated-lung-cancer-in-mice
#4
Fei Xu, Wenqiang Cui, Zhengxiao Zhao, Weiyi Gong, Ying Wei, Jiaqi Liu, Mihui Li, Qiuping Li, Chen Yan, Jian Qiu, Baojun Liu, Jingcheng Dong
Our previous studies have shown that Qing-Re-Huo-Xue (QRHX) formulae had significant anti-inflammatory effects in chronic airway diseases such as asthma and chronic obstructive lung disease. Here, we examined the effects of QRHX on lung cancer cell invasion and the potential associated mechanism(s), mainly polarization of macrophages in the tumor microenvironment. In vivo, QRHX both inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in mice with lung cancer. Further study indicated that QRHX inhibited cancer-related inflammation in tumor by decreasing infiltration of TAMs and IL-6 and TNF-α production and meanwhile decreased arginase 1 (Arg-1) expression and increased inducible NO synthase (iNOS) expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28629783/grp78-plays-an-integral-role-in-tumor-cell-inflammation-related-migration-induced-by-m2-macrophages
#5
Lichao Zhang, Zongwei Li, Guobin Ding, Xiaoqin La, Peng Yang, Zhuoyu Li
Macrophages are the main immune-competent cells that infiltrate in tumors. Tumor-associated macrophages (TAMs), termed M2 macrophages, facilitate tumor progress and promote metastasis. However, M2 macrophages always display an immunosuppressive phenotype, which is not in accordance with the tumor inflammatory microenvironment and inflammation-related metastasis. In this study, we established a macrophage polarization model with human monocytes and found that the conditioned medium from M2 macrophages increased GRP78 expression in tumor cells and facilitated tumor cell migration...
June 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28624450/%C3%AE-elemene-inhibits-tumor-promoting-effect-of-m2-macrophages-in-lung-cancer
#6
Xiaomu Yu, Maoyi Xu, Na Li, Zongjuan Li, Hongye Li, Shujuan Shao, Kun Zou, Lijuan Zou
Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene...
June 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28618326/inflammation-as-target-in-cancer-therapy
#7
REVIEW
Giulia Marelli, Antonio Sica, Luca Vannucci, Paola Allavena
Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies...
June 12, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28616398/new-photodynamic-therapy-with-next-generation-photosensitizers
#8
REVIEW
Hiromi Kataoka, Hirotada Nishie, Noriyuki Hayashi, Mamoru Tanaka, Akihiro Nomoto, Shigenobu Yano, Takashi Joh
Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate...
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28615091/-detection-and-analysis-of-phenotypes-of-tumor-associated-macrophages-in-mouse-model-of-spontaneous-breast-cancer
#9
Xiaojie Ren, Peng Ren, Song Luo, Quanbo Ji, Meng Xu, Ning Lu, Yan Wang
Objective To detect the phenotypic conversion of tumor-associated macrophages (TAMs) through analyzing the expression levels of the polarization-related genes. Methods We identified the spontaneous breast cancer mice by genotyping and characterized them into the early stage and the advanced stage groups according to their tumor size. Single cell suspension of the tumor tissues were obtained by mechanical methods and TAMs of different stages were sorted by flow cytometry. We measured the mRNA levels of M1 macrophages-related genes IL-1β, IL-27, IL-6, CD80, CD86 and M2 macrophages-related genes arginase 1 (Arg1), IL-10, interleukin 4 receptor α (IL-4Rα), macrophage mannose receptor 1 (Mrc1), chitinase-like 3 (Chil3/Ym1) by real-time quantitative PCR in order to analyze the phenotypic conversion of TAMs during the tumor progression...
June 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28608139/doxorubicin-hydrochloride-loaded-zymosan-polyethylenimine-biopolymeric-nanoparticles-for-dual-chemoimmunotherapeutic-intervention-in-breast-cancer
#10
Vivek K Pawar, Yuvraj Singh, Komal Sharma, Arpita Shrivastav, Abhisheak Sharma, Akhilesh Singh, Jaya Gopal Meher, Pankaj Singh, Kavit Raval, Himangshu K Bora, Dipak Datta, Jawahar Lal, Manish K Chourasia
OBJECTIVE: To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. METHOD: Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability...
June 12, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28602979/inhibition-of-cyp4a-by-a-novel-flavonoid-fla-16-prolongs-survival-and-normalizes-tumor-vasculature-in-glioma
#11
Chenlong Wang, Ying Li, Honglei Chen, Jie Zhang, Jing Zhang, Tian Qin, Chenfan Duan, Xuewei Chen, Yanzhuo Liu, Xiaoyang Zhou, Jing Yang
Glioblastomas rapidly become refractory to anti-VEGF therapies. We previously showed that cytochrome P450 (CYP) 4A-derived 20-hydroxyeicosatetraenoic acid (20-HETE) promotes angiogenesis. Here, we tested whether a novel flavonoid (FLA-16) prolongs survival and normalizes tumor vasculature in glioma through CYP4A inhibition. FLA-16 improved survival, reduced tumor burden, and normalized vasculature, accompanied with the decreased secretion of 20-HETE, VEGF and TGF-β in tumor-associated macrophages (TAMs) and endothelial progenitor cells (EPCs) in C6 and U87 gliomas...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28592924/suppression-of-endothelial-cell-migration-by-tumor-associated-macrophage-derived-exosomes-is-reversed-by-epithelial-ovarian-cancer-exosomal-lncrna
#12
Quanfeng Wu, Xiaoli Wu, Xiang Ying, Qinyi Zhu, Xinjing Wang, Lu Jiang, Xin Chen, Yueqian Wu, Xipeng Wang
OBJECTIVE: To study the mechanism by which epithelial ovarian cancer (EOC)-derived exosomes restore the migration of endothelial cells that is suppressed by TAM-derived exosomes. METHODS: Exosomes were isolated from TAMs in the ascites of patients with EOC. The effect of exosomes on the expression of endothelial cell miRNA was monitored by PCR. The miRNA mimics were transfected to explore their effects. Microarray data and literature searches were used to predict target genes and the impact of target gene pathways, and small interfering RNA was used to target these genes...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28591224/low-dose-glucocorticoids-suppresses-ovarian-tumor-growth-and-metastasis-in-an-immunocompetent-syngeneic-mouse-model
#13
Kai-Ti Lin, Shu-Pin Sun, Jui-I Wu, Lu-Hai Wang
Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B...
2017: PloS One
https://www.readbyqxmd.com/read/28590113/dacarbazine-loaded-hollow-mesoporous-silica-nanoparticles-grafted-with-folic-acid-for-enhancing-antimetastatic-melanoma-response
#14
Qianqian Liu, Nan Xu, Liping Liu, Jun Li, Yamin Zhang, Chen Shen, Khurram Shezad, Lianbin Zhang, Jintao Zhu, Juan Tao
Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28588582/nanoparticle-based-magnetic-resonance-imaging-on-tumor-associated-macrophages-and-inflammation
#15
REVIEW
Natalie J Serkova
The inflammatory response, mediated by tissue-resident or newly recruited macrophages, is an underlying pathophysiological condition for many diseases, including diabetes, obesity, neurodegeneration, atherosclerosis, and cancer. Paradoxically, inflammation is a double-edged sword in oncology. Macrophages are, generally speaking, the major drivers of inflammatory insult. For many solid tumors, high density of cells expressing macrophage-associated markers have generally been found in association with a poor clinical outcome, characterized by inflamed microenvironment, a high level of dissemination and resistance to conventional chemotherapies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588009/exosome-derived-mir-25-3p-and-mir-92a-3p-stimulate-liposarcoma-progression
#16
Lucia Casadei, Federica Calore, Chad J Creighton, Michele Guescini, Kara Batte, O Hans Iwenofu, Abeba Zewdu, Danielle Braggio, Kate Lynn Bill, Paolo Fadda, Francesca Lovat, Gonzalo Lopez, Pierluigi Gasparini, James L Chen, Raleigh D Kladney, Gustavo Leone, Dina Lev, Carlo M Croce, Raphael E Pollock
Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease...
June 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28586039/exosomes-derived-from-hypoxic-epithelial-ovarian-cancer-deliver-microrna-940-to-induce-macrophage-m2-polarization
#17
Xin Chen, Xiang Ying, Xinjing Wang, Xiaoli Wu, Qinyi Zhu, Xipeng Wang
Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28583114/the-peripheral-monocyte-count-is-associated-with-the-density-of-tumor-associated-macrophages-in-the-tumor-microenvironment-of-colorectal-cancer-a-retrospective-study
#18
Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Shigetomi Nakao, Shinji Matsutani, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated...
June 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28582845/elevated-lactate-dehydrogenase-ldh-can-be-a-marker-of-immune-suppression-in-cancer-interplay-between-hematologic-and-solid-neoplastic-clones-and-their-microenvironments
#19
Jennifer Ding, Judith E Karp, Ashkan Emadi
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28576927/overcoming-the-immunosuppressive-tumor-microenvironment-of-hodgkin-lymphoma-using-chimeric-antigen-receptor-t-cells
#20
Marco Ruella, Michael Klichinsky, Saad S Kenderian, Olga Shestova, Amy Ziober, Daniel O Kraft, Michael Feldman, Mariusz A Wasik, Carl H June, Saar Gill
Some patients with otherwise treatment-resistant Hodgkin lymphoma (HL) could benefit from chimeric antigen receptor T cell (CART) therapy. However, HL lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in HL, CART should target both malignant cells and the TME. We demonstrated CD123 on both HL cells and TME, including tumor-associated macrophages (TAM). In vitro, HL cells convert macrophages towards immunosuppressive TAM that inhibit T cell proliferation. In contrast, anti-CD123 CART recognized and killed TAM thus overcoming immunosuppression...
June 2, 2017: Cancer Discovery
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