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https://www.readbyqxmd.com/read/29456740/an-obligatory-anaerobic-salmonella-typhimurium-strain-redirects-m2-macrophages-to-the-m1-phenotype
#1
Mei Yang, Juan Xu, Qi Wang, An-Qin Zhang, Kun Wang
A genetically engineered Salmonella typhimurium strain that may be applied in the medically useful therapeutic strategy of using bacterial agents to target breast cancer in a tumor-bearing nude mouse model has been previously reported. Furthermore, immune cell accumulation in breast tumor types has been observed, particularly distributed in regions surrounding the bacteria. M2 macrophages are associated with breast cancer aggressiveness, whereas M1 macrophages are prone to devouring bacteria and killing cancer cells...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456737/distinctive-profiles-of-tumor-infiltrating-immune-cells-and-association-with-intensity-of-infiltration-in-colorectal-cancer
#2
Yugang Wu, Lei Yuan, Qicheng Lu, Haiyan Xu, Xiaozhou He
Tumor-infiltrating immune cells are heterogeneous and consist of characteristic compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit distinctive biological functions. The present study investigated the profile of infiltrating immune cells from surgically removed tumor tissues from patients with colorectal cancer. The characteristic transcription factors of Th1 and Th2 cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed. The results demonstrated that a marked increased number of Treg cells presented in tumor infiltrates when compared with non-tumor adjacent tissues...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456665/involvement-of-tweak-and-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-lupus-nephritis
#3
Fang Sun, Jian Teng, Pengfei Yu, Wenshuang Li, Jing Chang, Honglei Xu
Previous findings have identified that tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is associated with lupus nephritis (LN) activity status; however, the mechanism involved remains unclear. The present study aimed to investigate the roles of TWEAK and the nuclear factor (NF)-κB signaling pathway in LN. TWEAK levels in the blood and urine of patients with LN or non-LN systemic lupus erythematosus were measured by ELISA and compared with those in healthy controls. TWEAK expression and NF-κB transcriptional activity in the kidney were detected by western blotting, and Ki-67 and cluster of differentiation (CD) 68 expression were assessed using immunofluorescence...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456539/generation-of-human-immunosuppressive-myeloid-cell-populations-in-human-interleukin-6-transgenic-nog-mice
#4
Asami Hanazawa, Ryoji Ito, Ikumi Katano, Kenji Kawai, Motohito Goto, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29454748/fatty-acid-binding-protein-4-fabp4-overexpression-in-intratumoral-hepatic-stellate-cells-within-hepatocellular-carcinoma-with-metabolic-risk-factors
#5
Norimichi Chiyonobu, Shu Shimada, Yoshimitsu Akiyama, Kaoru Mogushi, Michiko Itoh, Keiichi Akahoshi, Satoshi Matsumura, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Takayoshi Suganami, Shoji Yamaoka, Yoshihiro Ogawa, Minoru Tanabe, Shinji Tanaka
Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC); however, tumor-specific biomarkers still remain unclear. We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, which develop HCC with obesity, insulin resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included mouse HCC and was etiologically associated with metabolic risk factors...
February 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29454317/oxidative-damage-and-response-to-bacillus-calmette-gu%C3%A3-rin-in-bladder-cancer-cells-expressing-sialyltransferase-st3gal1
#6
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Roberto Barbaro Forleo, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
BACKGROUND: Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown. METHODS: The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T , that express, respectively, either the sT or the T antigens...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29453519/tricurin-a-synergistic-formulation-of-curcumin-resveratrol-and-epicatechin-gallate-repolarizes-tumor-associated-macrophages-and-triggers-an-immune-response-to-cause-suppression-of-hpv-tumors
#7
Sumit Mukherjee, Rahman Hussaini, Richard White, Doaa Atwi, Angela Fried, Samay Sampat, Longzhu Piao, Quintin Pan, Probal Banerjee
Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29452207/glycogen-synthase-kinase-3%C3%AE-promotes-liver-innate-immune-activation-by-restraining-amp-activated-protein-kinase-activation
#8
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29450544/hla-class-i-antigen-expression-in-conjunctival-melanoma-is-not-associated-with-pd-l1-pd-1-status
#9
Jinfeng Cao, Niels J Brouwer, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd G van Duinen, Nadine E de Waard, Bruce R Ksander, Arend Mulder, Frans H J Claas, Mirjam H M Heemskerk, Martine J Jager
Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29450136/initiative-action-of-tumor-associated-macrophage-during-tumor-metastasis
#10
REVIEW
Saroj Singh, Neesha Mehta, Jiang Lilan, Meen Bahadur Budhthoki, Fu Chao, Li Yong
Tumor-associated macrophages (TAMs) are a significant component of the microenvironment of any solid tumors in the majority of cancers, associated with unfavorable prognosis. TAMs emerge as attractive targets for therapeutic strategies aimed at reprogramming their protumor phenotype into an effective antitumor activity. In this review article, we present an overview of mechanisms responsible for TAMs recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449276/immune-evasion-via-pd-1-pd-l1-on-nk-cells-and-monocyte-macrophages-is-more-prominent-in-hodgkin-lymphoma-than-dlbcl
#11
Frank Vari, David Arpon, Colm Keane, Mark S Hertzberg, Dipti Talaulikar, Sanjiv Jain, Qingyan Cui, Erica Han, Josh Tobin, Robert Bird, Donna Cross, Annette Hernandez, Clare Gould, Simone Birch, Maher K Gandhi
Much focus has been on the interaction of PD-L1 on malignant B-cells with PD-1 on effector T-cells in inhibiting anti-lymphoma immunity. We sought to establish the contribution of NK-cells and inhibitory CD163+ monocytes/macrophages in Hodgkin Lymphoma (cHL) and Diffuse Large B-cell Lymphoma (DLBCL). Levels of PD-1 on NK-cells were elevated in cHL relative to DLBCL. Notably, CD3- CD56hi CD16-ve NK-cells had substantially higher PD-1 expression relative to CD3- CD56dim CD16+ cells, and were expanded in blood and tissue, more marked in cHL than DLBCL patients...
February 15, 2018: Blood
https://www.readbyqxmd.com/read/29448000/bone-marrow-derived-fibrocytes-promote-stem-cell-like-properties-of-lung-cancer-cells
#12
Atsuro Saijo, Hisatsugu Goto, Mayuri Nakano, Atsushi Mitsuhashi, Yoshinori Aono, Masaki Hanibuchi, Hirohisa Ogawa, Hisanori Uehara, Kazuya Kondo, Yasuhiko Nishioka
Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14 + monocytes and have features of both macrophages and fibroblasts...
February 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29447241/selective-targeting-of-tumor-associated-macrophages-in-different-tumor-models
#13
Bianca Kakoschky, Thomas Pleli, Christian Schmithals, Stefan Zeuzem, Bernhard Brüne, Thomas J Vogl, Horst-Werner Korf, Andreas Weigert, Albrecht Piiper
Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma...
2018: PloS One
https://www.readbyqxmd.com/read/29445150/loss-of-ndrg2-in-liver-microenvironment-inhibits-cancer-liver-metastasis-by-regulating-tumor-associate-macrophages-polarization
#14
Mengyang Li, Xiaofeng Lai, Ying Zhao, Yuan Zhang, Minghui Li, Danxiu Li, Jing Kong, Yong Zhang, Pengyu Jing, Huichen Li, Hongyan Qin, Liangliang Shen, Libo Yao, Jipeng Li, Kefeng Dou, Jian Zhang
The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion of inhibitory factors, may be a potential therapeutic strategy for liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream-regulated gene 2) and verified its tumor suppressor role in multiple solid tumors, including colorectal cancer and hepatocellular carcinoma...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445088/cancer-cell-responses-to-hsp70-inhibitor-jg-98-comparison-with-hsp90-inhibitors-and-finding-synergistic-drug-combinations
#15
Julia A Yaglom, Yongmei Wang, Amy Li, Zhenghu Li, Stephano Monti, Ilya Alexandrov, Xiongbin Lu, Michael Y Sherman
Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors show anti-cancer activities affecting both cancer cells and tumor-associated macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect signaling pathways important for cancer development. Due to a prior report that depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their effects to effects of Hsp90 inhibitors...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440290/a-spatio-temporal-model-of-macrophage-mediated-drug-resistance-in-glioma-immunotherapy
#16
Yongjiang Zheng, Jiguang Bao, Qiyi Zhao, Tianshou Zhou, Xiaoqiang Sun
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#17
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29439934/suppressed-networks-of-inflammatory-mediators-characterize-chronic-venous-insufficiency
#18
Ulka Sachdev, Lena Vodovotz, Julie Bitner, Derek Barclay, Ruben Zamora, Jinling Yin, Richard L Simmons, Yoram Vodovotz
OBJECTIVE: Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects. METHODS: Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure...
February 10, 2018: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/29437708/expression-of-adipocyte-macrophage-fatty-acid-binding-protein-in-tumor-associated-macrophages-promotes-breast-cancer-progression
#19
Jiaqing Hao, Fei Yan, Yuwen Zhang, Ashley Triplett, Ying Zhang, Debra A Schultz, Yanwen Sun, Jun Zeng, Kevin A T Silverstein, Qi Zheng, David A Bernlohr, Margot P Cleary, Nejat K Egilmez, Edward Sauter, Shujun Liu, Jill Suttles, Bing Li
Tumor associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically-relevant markers for pro-tumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid binding protein (A-FABP) in TAM promotes breast cancer progression. While upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis...
February 6, 2018: Cancer Research
https://www.readbyqxmd.com/read/29437282/phagocytosis-of-antibody-opsonized-tumor-cells-leads-to-the-formation-of-a-discrete-vacuolar-compartment-in-macrophages
#20
Ramraj Velmurugan, Sreevidhya Ramakrishnan, Mingin Kim, Raimund J Ober, E Sally Ward
Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome...
February 13, 2018: Traffic
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