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https://www.readbyqxmd.com/read/29229677/apoptotic-cancer-cells-suppress-5-lipoxygenase-in-tumor-associated-macrophages
#1
Julia Ringleb, Elisabeth Strack, Carlo Angioni, Gerd Geisslinger, Dieter Steinhilber, Andreas Weigert, Bernhard Brüne
The enzyme 5-lipoxygenase (5-LO) is key in the synthesis of leukotrienes, which are potent proinflammatory lipid mediators involved in chronic inflammatory diseases including cancer. 5-LO is expressed in immune cells but also found in cancer cells. Although the role of 5-LO in tumor cells is beginning to emerge, with the notion that tumor-promoting functions are attributed to its products, the function of 5-LO in the tumor microenvironment remains unclear. To understand the role of 5-LO and its products in the tumor microenvironment, we analyzed its expression and function in tumor-associated macrophages (TAMs)...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29228668/tsc-22-inhibits-csf-1r-function-and-induces-apoptosis-in-cervical-cancer
#2
Min-Ji Cho, Ji-Yeon Lee, Min-Gwan Shin, Hyun-Ji Kim, Yu-Joung Choi, Seung Bae Rho, Boh-Ram Kim, Ik Soon Jang, Seung-Hoon Lee
Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-β stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228548/macrophage-depletion-through-colony-stimulating-factor-1-receptor-pathway-blockade-overcomes-adaptive-resistance-to-anti-vegf-therapy
#3
Yasmin A Lyons, Sunila Pradeep, Sherry Y Wu, Monika Haemmerle, Jean M Hansen, Michael J Wagner, Alejandro Villar-Prados, Archana S Nagaraja, Robert L Dood, Rebecca A Previs, Wei Hu, Yang Zhao, Duncan H Mak, Zhilan Xiao, Brenda D Melendez, Gregory A Lizee, Imelda Mercado-Uribe, Keith A Baggerly, Patrick Hwu, Jinsong Liu, Willem W Overwijk, Robert L Coleman, Anil K Sood
Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228085/immunolocalization-of-cd163-tumor-associated-macrophages-and-symmetric-proliferation-of-ki-67-as-biomarkers-to-differentiate-new-different-grades-of-laryngeal-dysplasia
#4
Caili Su, Shuangshuang Jia, Honggang Liu
Objectives: To evaluate CD163+ tumor-associated macrophages (TAMs), Ki-67, and cyclin D1 to differentiate laryngeal dysplasia in the 2017 World Health Organization classification. Methods: Immunohistochemistry for CD163, Ki-67, and cyclin D1 was performed using paraffin-embedded specimens. CD163+ TAMs infiltrating the epithelium were estimated. Ki-67 and cyclin D1 were evaluated in four parts of the epithelium-basal, parabasal, middle third, and upper third layers...
December 7, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29227538/abberent-expression-of-nor1-protein-in-tumor-associated-macrophages-contributes-to-the-development-of-den-induced-hepatocellular-carcinoma
#5
Shengnan Chen, Pan Zheng, Wei Wang, Mei Yi, Pan Chen, Jing Cai, Junjun Li, Qian Peng, Yuanyuan Ban, Ying Zhou, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Guiyuan Li, Bo Xiang
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the sixth most common lethal cancer worldwide. Recent evidences demonstrated that oxidored nitro domain containing protein 1(NOR1), a putative tumor suppressor gene, is overexpressed in human HCC tissues. However, the role of NOR1 in HCC development remains unclear. Here, we described that NOR1 protein level is elevated in HCC and is associated with poorer clinical outcome. However, ecotopic overexpression of NOR1 protein in human HCC cell line HepG2 cells had no effect on cells proliferation, migration and clonality...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29225138/9-hydroxycanthin-6-one-isolated-from-stem-bark-of-ailanthus-altissima-induces-ovarian-cancer-cell-apoptosis-and-inhibits-the-activation-of-tumor-associated-macrophages
#6
Miran Jeong, Hye Mi Kim, Ji-Hye Ahn, Kyung-Tae Lee, Dae Sik Jang, Jung-Hye Choi
The stem bark of Ailanthus altissima is used in traditional medicine in Asia to treat a variety of diseases, including cancer. The aim of this study was to identify compounds with tumoricidal activity from A. altissima stem bark and to investigate their mechanisms of action. Among the 13 compounds isolated from the ethyl acetate fraction of A. altissima stem bark, the β-carboline alkaloid 9-hydroxycanthin-6-one had potent cytotoxicity in all three ovarian cancer cell types examined. 9-Hydroxycanthin-6-one induced apoptosis through the activation of caspases-3, -8, and -9...
December 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29224225/down-regulation-of-15-pgdh-by-interleukin-1-beta-from-activated-macrophages-leads-to-poor-prognosis-in-pancreatic-cancer
#7
Kota Arima, Yoshihiro Komohara, Luke Bu, Masayo Tsukamoto, Rumi Itoyama, Keisuke Miyake, Tomoyuki Uchihara, Yoko Ogata, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Yo-Ichi Yamashita, Hideo Baba, Takatsugu Ishimoto
Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE2 ). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29222346/adiposity-inflammation-and-breast-cancer-pathogenesis-in-asian-women
#8
Neil M Iyengar, I-Chun Chen, Xi K Zhou, Dilip D Giri, Domenick J Falcone, Lisle A Winston, Hanhan Wang, Samantha Williams, Yen-Shen Lu, Tsu-Hsin Hsueh, Ann-Lii Cheng, Clifford A Hudis, Ching-Hung Lin, Andrew J Dannenberg
Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus western countries...
December 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29221953/antitumor-action-of-3-bromopyruvate-implicates-reorganized-tumor-growth-regulatory-components-of-tumor-milieu-cell-cycle-arrest-and-induction-of-mitochondria-dependent-tumor-cell-death
#9
Saveg Yadav, Praveen Kumar Kujur, Shrish Kumar Pandey, Yugal Goel, Babu Nandan Maurya, Ashish Verma, Ajay Kumar, Rana Pratap Singh, Sukh Mahendra Singh
Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death...
December 5, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29220404/pymt-maclow-a-novel-inducible-murine-model-for-determining-the-role-of-cd68-positive-cells-in-breast-tumor-development
#10
Robin M H Rumney, Seth B Coffelt, Terence A Neale, Sandeep Dhayade, Gillian M Tozer, Gaynor Miller
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development...
2017: PloS One
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#11
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29218457/phenotypical-change-of-tumor-associated-macrophages-in-metastatic-lesions-of-clear-cell-renal-cell-carcinoma
#12
Takanobu Motoshima, Yuji Miura, Nanako Wakigami, Natsuki Kusada, Toshimi Takano, Naoko Inoshita, Toshikazu Okaneya, Yutaka Sugiyama, Tomomi Kamba, Motohiro Takeya, Yoshihiro Komohara
Macrophages are the main immune cells of the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). A high density of CD163+ or CD204+ tumor-associated macrophages (TAMs), rather than the density of total TAMs, is known to be linked to poor clinical outcome. In the present study, we investigated the phenotypical differences between the paired primary and metastatic lesions in ccRCC cases. Using immunostaining, the densities of CD163+ and CD204+ TAMs in metastatic lesions were found to be significantly lower compared to primary lesions, although the total number of TAMs was increased in metastatic lesions...
December 7, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29218246/angiopoietin-like-protein-2-facilitates-non-small-cell-lung-cancer-progression-by-promoting-the-polarization-of-m2-tumor-associated-macrophages
#13
Xiaojuan Wei, Siyue Nie, Hui Liu, Jingyu Sun, Jie Liu, Juan Li, Shuyan Li, Shuyun Wang, Shuyi Han, Jun Wang, Yuping Sun
The functional phenotypes (M1 and M2) of tumor-associated macrophages (TAMs) are influenced by the tumor microenvironment (TME) and contribute greatly to the development of non-small cell lung cancer (NSCLC). However, the molecular mechanisms for TAM polarization remain unclear. Angiopoietin-like protein 2 (Angptl2) is involved in tumor progression. In this study, Angptl2 expression was aberrantly increased in NSCLC cells and positively correlated with TAM infiltration, tumor size and poor patient survival...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29218108/the-synergistic-effect-of-esophageal-squamous-cell-carcinoma-kyse150-cells-and-m2-macrophages-on-lymphatic-endothelial-cells
#14
Miao-Miao Sun, Lu-Lu He, Hong-Xin Zhang, Na Wei, Wei-Wei Wang, Guo-Zhong Jiang, Zheng-Yang Wang, Dong-Mei Zhao, Kui-Sheng Chen
Objective: This study aimed to investigate whether tumor-associated macrophages (TAMs) and esophageal squamous cell carcinoma (ESCC) cells could synergistically influence the generation of lymphatic vessels via the VEGF-C/VEGFR-3 signaling pathway and to address its mechanism. Methods: M2 macrophages were sorted with immunomagnetic beads and induced in vitro. VEGF-C siRNA plasmids were constructed and transfected into M2 macrophages and the ESCC cell line KYSE150. Different conditioned culture media before and after transfection were collected and classified into different groups for culturing ESCC-associated lymphatic endothelial cells (ESCC-LECs)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217840/the-role-of-anxious-distress-in-immune-dysregulation-in-patients-with-major-depressive-disorder
#15
Roxanne Gaspersz, Femke Lamers, Gayle Wittenberg, Aartjan T F Beekman, Albert M van Hemert, Robert A Schoevers, Brenda W J H Penninx
Although depression with anxious distress appears to be a clinically relevant subtype of major depressive disorder (MDD), whether it involves specific pathophysiology remains unclear. Inflammation has been implicated, but not comprehensively studied. We examined within a large MDD sample whether anxious distress and related anxiety features are associated with differential basal inflammation and innate cytokine production capacity. Data are from 1078 MDD patients from the Netherlands Study of Depression and Anxiety...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29217822/hepatocyte-toll-like-receptor-4-mediates-lipopolysaccharide-induced-hepcidin-expression
#16
Yong-Soo Lee, Yong-Hoon Kim, Yoon Seok Jung, Ki-Sun Kim, Don-Kyu Kim, Soon-Young Na, Ji-Min Lee, Chul-Ho Lee, Hueng-Sik Choi
Hepcidin expression is induced by inflammatory molecules such as lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes directly respond to LPS, the molecular mechanism underlying toll-like receptor (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we show that LPS can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF), we demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29217508/il-1%C3%AE-interleukin-1%C3%AE-and-tnf-%C3%AE-tumor-necrosis-factor-%C3%AE-impact-abdominal-aortic-aneurysm-formation-by-differential-effects-on-macrophage-polarization
#17
Rishi Batra, Melissa K Suh, Jeffrey S Carson, Matthew A Dale, Trevor M Meisinger, Matthew Fitzgerald, Patrick J Opperman, Jiangtao Luo, Iraklis I Pipinos, Wanfen Xiong, B Timothy Baxter
OBJECTIVE: Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation...
December 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#18
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212557/preconditioning-of-murine-mesenchymal-stem-cells-synergistically-enhanced-immunomodulation-and-osteogenesis
#19
Tzuhua Lin, Jukka Pajarinen, Akira Nabeshima, Laura Lu, Karthik Nathan, Eemeli Jämsen, Zhenyu Yao, Stuart B Goodman
BACKGROUND: Mesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation...
December 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29212030/loss-of-caveolin-1-in-metastasis-associated-macrophages-drives-lung-metastatic-growth-through-increased-angiogenesis
#20
Ward Celus, Giusy Di Conza, Ana Isabel Oliveira, Manuel Ehling, Bruno M Costa, Mathias Wenes, Massimiliano Mazzone
Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-suppressive functions. However, the role of Cav1 in bone-marrow-derived cells is unknown. Here, we describe Cav1 as an anti-metastatic regulator in mouse models of lung and breast cancer pulmonary metastasis...
December 5, 2017: Cell Reports
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