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https://www.readbyqxmd.com/read/29791764/synergy-between-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-and-radiotherapy-in-cancer
#1
Guodong Huang, Limei Yin, Jie Lan, Ruizhan Tong, Mengqian Li, Feifei Na, Xianming Mo, Chong Chen, Jianxin Xue, You Lu
ANGIOGENESIS AND INFLAMMATION ARE CRUCIAL PROCESSES, THROUGH WHICH THE: tumor microenvironment (TME) influences tumor progression. In this STUDY, WE REVEALED THAT PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR Γ (PPARΓ) IS: NOT ONLY EXPRESSED IN CT26 AND 4T1 TUMOR CELL LINES BUT ALSO IN CELLS OF TME,: including endothelial cells and tumor-associated macrophages (TAMs). In addition, WE DEMONSTRATED THAT ROSIGLITAZONE MAY INDUCE TUMOR VESSEL NORMALIZATION AND REDUCE: TAM infiltration. Additionally, 4T1 and CT26 tumor-bearing mice treated with ROSIGLITAZONE IN COMBINATION WITH RADIOTHERAPY DISPLAYED A SIGNIFICANT REDUCTION IN: lesion size and lung metastasis...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29789715/shared-and-independent-functions-of-apkc%C3%AE-and-par3-in-skin-tumorigenesis
#2
Susanne Vorhagen, Dominik Kleefisch, Oana-Diana Persa, Annika Graband, Alexandra Schwickert, Michael Saynisch, Michael Leitges, Carien M Niessen, Sandra Iden
The polarity proteins Par3 and aPKC are key regulators of processes altered in cancer. Par3/aPKC are thought to dynamically interact with Par6 but increasing evidence suggests that aPKC and Par3 also exert complex-independent functions. Whereas aPKCλ serves as tumor promotor, Par3 can either promote or suppress tumorigenesis. Here we asked whether and how Par3 and aPKCλ genetically interact to control two-stage skin carcinogenesis. Epidermal loss of Par3, aPKCλ, or both, strongly reduced tumor multiplicity and increased latency but inhibited invasion to similar extents, indicating that Par3 and aPKCλ function as a complex to promote tumorigenesis...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789416/macrophage-derived-granulin-drives-resistance-to-immune-checkpoint-inhibition-in-metastatic-pancreatic-cancer
#3
Michael C Schmid, Valeria Quaranta, Carolyn Rainer, Sebastian Rune Nielsen, Meirion Llŷr Raymant, Muhammad S Ahmed, Dannielle D Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H Palmer, David A Tuveson, Ainhoa Mielgo
The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29787979/genome-wide-analysis-reveals-tnfaip8l2-as-an-immune-checkpoint-regulator-of-inflammation-and-metabolism
#4
Ting Li, Wei Wang, Shunyou Gong, Honghong Sun, Huqin Zhang, An-Gang Yang, Youhai H Chen, Xinyuan Li
The interplay between inflammation and metabolism is widely recognized, yet the underlying molecular mechanisms remain poorly characterized. Using experimental database mining and genome-wide gene expression profiling methods, we found that in contrast to other TNFAIP8 family members, TNFAIP8L2 (TIPE2) was preferentially expressed in human myeloid cell types. In addition, Tnfaip8l2 expression drastically decreased in lipopolysaccharide (LPS)-stimulated macrophages. Consequently, Tnfaip8l2 deficiency led to heightened expression of genes that were enriched for leukocyte activation and lipid biosynthesis pathways...
May 19, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29787282/regulating-the-uptake-of-viral-nanoparticles-in-macrophage-and-cancer-cells-by-via-a-ph-switch
#5
Hamilton Lee, Candace E Benjamin, Chance M Nowak, Lana Tuong, Raymond P Welch, Zhuo Chen, Madushani Dharmarwardana, Kyle Murray, Leonidas Bleris, Sheena D'Arcy, Jeremiah J Gassensmith
Controlling the uptake of nanomaterials into phagocytes is a challenging problem. We describe an approach to inhibit the cellular uptake by macrophages and HeLa cells of nano-particles derived from bacteriophage Qβ by conjugating negatively charged terminal hexanoic acid moieties onto its surface. Additionally, we show hydrazone linkers can be installed between the surface of Qβ and the terminal hexa-noic acid moieties, resulting in a pH-responsive conjugate that, in acidic conditions, can release the terminal hexanoic acid moiety and allow for the uptake of the Qβ nanoparti-cle...
May 22, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#6
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29783929/modulation-the-crosstalk-between-tumor-associated-macrophages-and-non-small-cell-lung-cancer-to-inhibit-tumor-migration-and-invasion-by-ginsenoside-rh2
#7
Honglin Li, Nan Huang, Weikang Zhu, Jianchun Wu, Xiaohui Yang, Wenjing Teng, Jianhui Tian, Zhihong Fang, Yingbin Luo, Min Chen, Yan Li
BACKGROUND: Tumor-associated macrophages (TAMs) play a critical role in modulating the tumor microenvironment and promote tumor metastases. Our studies have demonstrated that ginsenoside Rh2 (G-Rh2), a monomeric compound extracted from ginseng, is a promising anti-tumor agent in lung cancer cells. However, it remains unclear whetherG-Rh2 can modulate the differentiation of TAMs and its interaction with tumor microenvironment. In this study, we investigated how G-Rh2 regulates the phenotype of macrophages and affects the migration of non-small cell lung cancer (NSCLC) cells...
May 22, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29780684/a-new-insight-into-identification-of-in-silico-analysis-of-natural-compounds-targeting-gpr120
#8
Nagaraju Chinthakunta, Srinivasulu Cheemanapalli, Surekha Chinthakunta, C M Anuradha, Suresh Kumar Chitta
G-protein coupled receptor (GPR120) is an omega-3 fatty acid receptor that inhibits macrophage-induced tissue inflammation. Recent studies revealed GPR120 promotes colorectal carcinoma through modulation of VEGF, IL-8, PGE2, and NF-kB expression. However, three-dimensional structure of GPR120 is not yet available in Protein Data Bank (PDB). In the present study, we focused on a 3-D structural model of GPR120 has been constructed using homology modeling techniques. The structural quality of the predicted GPR120 model was verified using Procheck, Whatif, ProSA, and Verify 3D...
2018: Network Modeling and Analysis in Health Informatics and Bioinformatics
https://www.readbyqxmd.com/read/29780505/macrophage-mediated-delivery-of-light-activated-nitric-oxide-prodrugs-with-spatial-temporal-and-concentration-control
#9
Michael A Evans, Po-Ju Huang, Yuji Iwamoto, Kelly N Ibsen, Emory M Chan, Yutaka Hitomi, Peter C Ford, Samir Mitragotri
Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+ -doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780388/regulation-of-hematopoietic-cell-development-and-function-through-phosphoinositides
#10
REVIEW
Mila Elich, Karsten Sauer
One of the most paramount receptor-induced signal transduction mechanisms in hematopoietic cells is production of the lipid second messenger phosphatidylinositol(3,4,5)trisphosphate (PIP3 ) by class I phosphoinositide 3 kinases (PI3K). Defective PIP3 signaling impairs almost every aspect of hematopoiesis, including T cell development and function. Limiting PIP3 signaling is particularly important, because excessive PIP3 function in lymphocytes can transform them and cause blood cancers. Here, we review the key functions of PIP3 and related phosphoinositides in hematopoietic cells, with a special focus on those mechanisms dampening PIP3 production, turnover, or function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29780249/-in-vivo-mr-imaging-of-tumor-associated-macrophages-the-next-frontier-in-cancer-imaging
#11
REVIEW
Runze Yang, Susobhan Sarkar, V Wee Yong, Jeff F Dunn
There is a complex interaction between cancer and the immune system. Tumor-associated macrophages (TAMs) can be subverted by the cancer to adopt a pro-tumor phenotype to aid tumor growth. These anti-inflammatory, pro-tumor TAMs have been shown to contribute to a worsened outcome in several different types of cancer. Various strategies aimed at combating the pro-tumor TAMs have been developed. Several therapies, such as oncolytic viral therapy and high-intensity focused ultrasound, have been shown to stimulate TAMs and suppress tumor growth...
2018: Magnetic Resonance Insights
https://www.readbyqxmd.com/read/29777109/tak1-mediates-microenvironment-triggered-autocrine-signals-and-promotes-triple-negative-breast-cancer-lung-metastasis
#12
Oihana Iriondo, Yarong Liu, Grace Lee, Mostafa Elhodaky, Christian Jimenez, Lin Li, Julie Lang, Pin Wang, Min Yu
Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer that has limited therapeutic options. Thus, developing novel treatments for metastatic TNBC is an urgent need. Here, we show that nanoparticle-mediated delivery of transforming growth factor-β1-activated kinase-1 (TAK1) inhibitor 5Z-7-Oxozeaenol can inhibit TNBC lung metastasis in most animals tested. P38 is a central signal downstream of TAK1 in TNBC cells in TAK1-mediated response to multiple cytokines. Following co-culturing with macrophages or fibroblasts, TNBC cells express interleukin-1 (IL1) or tumor necrosis factor-α (TNFα), respectively...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777034/membrane-fluctuations-and-acidosis-regulate-cooperative-binding-of-marker-of-self-cd47-with-macrophage-checkpoint-receptor-sirp%C3%AE
#13
Jan Steinkühler, Bartosz Różycki, Cory Alvey, Reinhard Lipowsky, Thomas R Weikl, Rumiana Dimova, Dennis E Discher
Cell-cell interactions that result from membrane proteins binding weakly in trans can cause accumulations in cis that suggest cooperativity and thereby an acute sensitivity to environmental factors. The ubiquitous "marker of self" protein CD47 binds weakly to SIRPα on a macrophage, which leads to accumulation of SIRPα at a phagocytic synapse and ultimately to inhibition of engulfment of 'self' cells - including cancer cells. We reconstituted this macrophage checkpoint with CD47-GFP displayed on giant vesicles generated from plasma membranes and then imaged vesicles adhering to SIRPα immobilized on a surface...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29776955/high-fat-diet-induced-inflammation-accelerates-prostate-cancer-growth-via-il6-signaling
#14
Takuji Hayashi, Kazutoshi Fujita, Satoshi Nojima, Yujiro Hayashi, Kosuke Nakano, Yu Ishizuya, Cong Wang, Yoshiyuki Yamamoto, Toshiro Kinouchi, Kyosuke Matsuzaki, Kentaro Jingushi, Taigo Kato, Atsunari Kawashima, Akira Nagahara, Takeshi Ujike, Motohide Uemura, Maria Del Carmen Rodriguez Pena, Jennifer B Gordetsky, Eiichi Morii, Kazutake Tsujikawa, George J Netto, Norio Nonomura
OBJECTIVE: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. MATERIALS AND METHODS: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+; Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29773403/synthesis-of-chitin-glucan-aldehyde-quercetin-conjugate-and-evaluation-of-anticancer-and-antioxidant-activities
#15
Anu Singh, P K Dutta, Hridyesh Kumar, Amit Kumar Kureel, Ambak Kumar Rai
In the present study, we have synthesized chitin-glucan-aldehyde-quercetin (chi-glu-ald-que) conjugate via condensation reaction. Synthesis of chitin-glucan-aldehyde (chi-glu-ald) complex was facilitated by the oxidation of chitin-glucan (chi-glu) complex. Formation of conjugate was confirmed by Proton nuclear magnetic resonance spectroscopy (1 H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Morphological studies showed that after grafting of quercetin, several changes on surface were depicted and a more crystalline nature was observed...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#16
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772561/thyroid-cancer-phenotypes-in-relation-to-inflammation-and-autoimmunity
#17
Loredana Pagano, Chiara Mele, Maria Teresa Sama, Marco Zavattaro, Marina Caputo, Lucrezia De Marchi, Samuele Paggi, Flavia Prodam, Gianluca Aimaretti, Paolo Marzullo
Thyroid cancer represents the most frequent endocrine neoplasm and is epidemiologically linked to a growing incidence worldwide, which is only in part explained by the increased detection of small cancers in a preclinical stage. Understanding the molecular pathogenesis of well-differentiated thyroid cancers and poorly-differentiated thyroid cancers has prompted interest into the identification of crucial signaling pathways and molecular derangements related to genetic and epigenetic alterations. Increasing attention has been recently focused on inflammation and immunity as major culprit mechanisms involved in thyroid tumourigenesis, through the detection of activated immune cells, pro-inflammatory cytokines, as well as signal integrations between inflammatory and proliferative pathways within the thyroid tumour micro-environment...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29771951/antitumor-antioxidant-and-anti-inflammatory-activities-of-kaempferol-and-its-corresponding-glycosides-and-the-enzymatic-preparation-of-kaempferol
#18
Jingqiu Wang, Xianying Fang, Lin Ge, Fuliang Cao, Linguo Zhao, Zhenzhong Wang, Wei Xiao
Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells...
2018: PloS One
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#19
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771377/alternative-splicing-analysis-in-human-monocytes-and-macrophages-reveals-mbnl1-as-major-regulator
#20
Hongfei Liu, Paolo A Lorenzini, Fan Zhang, Shaohai Xu, Mei Su M Wong, Jie Zheng, Xavier Roca
We report the detailed transcriptomic profiles of human innate myeloid cells using RNA sequencing. Monocytes migrate from blood into infected or wounded tissue to differentiate into macrophages, and control inflammation via phagocytosis or cytokine secretion. We differentiated culture primary monocytes with either GM- or M-CSF to obtain pro- or anti-inflammatory macrophages, and respectively activated them with either LPS/IFNγ or anti-inflammatory cytokines. We also treated the THP-1 monocytic cell line with PMA and similar cytokines to mimic differentiation and activation...
May 16, 2018: Nucleic Acids Research
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