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https://www.readbyqxmd.com/read/28742795/cancer-associated-fibroblasts-promote-bone-invasion-in-oral-squamous-cell-carcinoma
#1
A A Elmusrati, A E Pilborough, S A Khurram, D W Lambert
BACKGROUND: The molecular mechanisms involved in the invasion of bone by oral squamous cell carcinomas (OSCC) are poorly understood, and little is known about the role of cancer-associated fibroblasts (CAF), the presence of which confers a poor prognosis. METHODS: Clinicopathological data from 277 OSCC cases involving bone resections were reviewed, and 32 cases thoroughly analysed histologically. Immunohistochemistry was used to examine αSMA, RANKL and OPG. Western blotting and qPCR were used to assess myofibroblast (CAF-like) differentiation, RANKL and OPG expression in vitro, and RANKL secretion was analysed by ELISA...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28740576/the-chemokine-scavenging-receptor-d6-ackr2-is-a-target-of-mir-146a-in-thyroid-cancer
#2
Francesco Pacifico, Alessio Lepore, Stefano Mellone, Luca Sanguigno, Giorgia Federico, Adelaide Greco, Arturo Brunetti, Antonio Leonardi
We have previously shown that miR-146a, a NF-κB-regulated microRNA, is strongly expressed in human specimens and cell lines derived from anaplastic thyroid carcinomas (ATC) where it mediates some of the NF-κB pro-tumorigenic functions. By using a bioinformatic analysis, we identified the chemokine scavenger receptor D6/ ACKR2 as a target of miR146a in human ATC. We found that the expression of D6/ ACKR2 was up-regulated in miR-146a-null ATC cell lines and that the 3' UTR of D6/ ACKR2 mRNA was able to inhibit its expression in parental, but not in miR-146a-null ATC cells...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28739604/s1pr1-on-tumor-associated-macrophages-promotes-lymphangiogenesis-and-metastasis-via-nlrp3-il-1%C3%AE
#3
Benjamin Weichand, Rüdiger Popp, Sarah Dziumbla, Javier Mora, Elisabeth Strack, Eiman Elwakeel, Ann-Christin Frank, Klaus Scholich, Sandra Pierre, Shahzad N Syed, Catherine Olesch, Julia Ringleb, Bilge Ören, Claudia Döring, Rajkumar Savai, Michaela Jung, Andreas von Knethen, Bodo Levkau, Ingrid Fleming, Andreas Weigert, Bernhard Brüne
Metastasis is the primary cause of cancer death. The inflammatory tumor microenvironment contributes to metastasis, for instance, by recruiting blood and lymph vessels. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1) alone in CD11b(hi) CD206(+) TAMs infiltrating mouse breast tumors prevents pulmonary metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also observed in the nonrelated methylcholanthrene-induced fibrosarcoma model...
July 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28739368/andrographolide-induces-oxidative-stress-dependent-cell-death-in-unicellular-protozoan-parasite-trypanosoma-brucei
#4
Malabika Banerjee, Debaprasad Parai, Pranab Dhar, Manab Roy, Rajib Barik, Subrata Chattopadhyay, Samir Kumar Mukherjee
African sleeping sickness is a parasitic disease in humans and livestock caused by Trypanosoma brucei throughout sub-Saharan Africa. Absence of appropriate vaccines and prevalence of drug resistance proclaim that a new way of therapeutic interventions is essential against African trypanosomiasis. In the present study, we have looked into the effect of andrographolide (andro), a diterpenoid lactone from Andrographis paiculata on Trypanosoma brucei PRA 380. Although andro has been recognized as a promosing anti-cancer drug, its usefulness against Trypanosoma spp remained unexplored...
July 21, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28738674/complex-consisting-of-%C3%AE-glucan-and-antigenic-peptides-with-cleavage-site-for-glutathione-and-aminopeptidases-induces-potent-cytotoxic-t-lymphocytes
#5
Shinichi Mochizuki, Hiromi Morishita, Kazuo Sakurai
The efficient induction of antigen-specific immune responses requires not only promotion of the uptake of antigens and adjuvant molecules into antigen-presenting cells, but also control of their intracellular behavior. We previously demonstrated that the β-glucan schizophyllan (SPG) can form complexes with CpG oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses. In this study, we prepared various conjugates comprising antigenic peptide (OVA257-264) and dA40, and made complexes with SPG...
July 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28738534/high-expression-of-cd47-predicts-adverse-prognosis-in-chinese-patients-and-suppresses-immune-response-in-melanoma
#6
Wenhua Fu, Jisen Li, Wei Zhang, Peng Li
BACKGROUND: Cluster of differentiation 47 (CD47) negatively regulates macrophage phagocytosis and is correlated with adverse survival of multiple cancers. In melanoma patients, especially in Chinese melanoma patients, its prognostic value is unclear. In this study, we aim to study the prognostic value of CD47 in a Chinse melanoma patient cohort and its immunomodulation roles in mouse model. METHOD: 164 melanoma tissue specimens were collected. The expression of CD47 in these clinical samples was examined by immunohistochemistry staining (IHC)...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28737512/thrombin-promotes-diet-induced-obesity-through-fibrin-driven-inflammation
#7
Anna K Kopec, Sara R Abrahams, Sherry Thornton, Joseph S Palumbo, Eric S Mullins, Senad Divanovic, Hartmut Weiler, A Phillip Owens, Nigel Mackman, Ashley Goss, Joanne van Ryn, James P Luyendyk, Matthew J Flick
Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737175/natural-variation-of-macrophage-activation-as-disease-relevant-phenotype-predictive-of-inflammation-and-cancer-survival
#8
Konrad Buscher, Erik Ehinger, Pritha Gupta, Akula Bala Pramod, Dennis Wolf, George Tweet, Calvin Pan, Charles D Mills, Aldons J Lusis, Klaus Ley
Although mouse models exist for many immune-based diseases, the clinical translation remains challenging. Most basic and translational studies utilize only a single inbred mouse strain. However, basal and diseased immune states in humans show vast inter-individual variability. Here, focusing on macrophage responses to lipopolysaccharide (LPS), we use the hybrid mouse diversity panel (HMDP) of 83 inbred strains as a surrogate for human natural immune variation. Since conventional bioinformatics fail to analyse a population spectrum, we highlight how gene signatures for LPS responsiveness can be derived based on an Interleukin-12β and arginase expression ratio...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28734227/continuous-delivery-of-neutralizing-antibodies-elevate-ccl2-levels-in-mice-bearing-mcf10ca1d-breast-tumor-xenografts
#9
Min Yao, Curtis Smart, Qingting Hu, Nikki Cheng
Chemokines are small soluble molecules that play critical roles in wound healing, infection, and cancer progression. In particular, overexpression of the C-C motif chemokine ligand 2 (CCL2) in multiple cancer types correlates with poor patient prognosis. Animal studies have shown that CCL2 signals to macrophages and breast cancer cells to promote tumor growth, invasion, and metastasis, indicating that CCL2 is a promising therapeutic target. However, the effectiveness of human-specific neutralizing antibodies has not been fully evaluated...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734132/high-dimensional-single-cell-mapping-of-cerium-distribution-in-the-lung-immune-microenvironment-of-an-active-smoker
#10
Adeeb H Rahman, Yonit Lavin, Soma Kobayashi, Andrew Leader, Miriam Merad
BACKGROUND: Mass cytometry leverages inductively coupled mass spectrometry to perform high dimensional single cell analyses using antibodies tagged with rare earth isotopes that are considered to be largely absent in biological samples. We have recently noted an unusual exception to this rule while analyzing tissue samples from patients undergoing surgical resection for early stage lung cancer, and here we present a detailed cytometric characterization of cerium in a clinical patient sample...
July 22, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28733709/il-4-blockade-alters-the-tumor-microenvironment-and-augments-the-response-to-cancer-immunotherapy-in-a-mouse-model
#11
Shuku-Ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka
Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes...
July 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28733560/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#12
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732227/atm-supports-gammaherpesvirus-replication-by-attenuating-type-i-interferon-pathway
#13
Eric J Darrah, Kyle P Stoltz, Mitchell Ledwith, Vera L Tarakanova
Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages...
July 18, 2017: Virology
https://www.readbyqxmd.com/read/28731284/the-rna-binding-protein-hur-inhibits-expression-of-ccl5-and-limits-recruitment-of-macrophages-into-tumors
#14
Thilo F Brauß, Sofia Winslow, Sebastian Lampe, Anica Scholz, Andreas Weigert, Nathalie Dehne, Kristoffer von Stedingk, Tobias Schmid, Bernhard Brüne
The RNA-binding protein HuR promotes tumor growth by affecting proliferation, metastasis, apoptosis, and angiogenesis. Although immune cells, especially tumor-associated macrophages, are critical components of the tumor stroma, the influence of HuR in tumors on the recruitment of immune cells remains poorly understood. In the present study, we therefore aimed to elucidate the impact of tumor cell HuR on the interaction between tumor cells and macrophages. To this end, we stably depleted HuR in human MCF-7 breast cancer cells...
July 21, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28730338/jagged1-promotes-aromatase-inhibitor-resistance-by-modulating-tumor-associated-macrophage-differentiation-in-breast-cancer-patients
#15
Hang Liu, Jingxuan Wang, Minghui Zhang, Qijia Xuan, Zhipeng Wang, Xin Lian, Qingyuan Zhang
PURPOSE: Endocrine resistance limits the efficacy of anti-estrogen therapies. Notch signaling is involved in modulating tumor-associated macrophage (TAM) differentiation and is upregulated in endocrine-resistant breast cancer cells. Here, we analyzed the role of Jagged1 in the regulation of TAM polarization to investigate whether the Jagged1-Notch pathway promotes the acquisition of aromatase inhibitor (AI) resistance by upregulating TAM infiltration. METHODS: The Jagged1 expression levels and M2 TAM infiltration density, in 203 tumor samples from ER-positive postmenopausal patients, who received AI treatment, were evaluated by immunohistochemical staining and the results were compared with clincopathological parameters and survival...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28729694/paracrine-cyclooxygenase-2-activity-by-macrophages-drives-colorectal-adenoma-progression-in-the-apc-min-mouse-model-of-intestinal-tumorigenesis
#16
Mark A Hull, Richard J Cuthbert, C W Stanley Ko, Daniel J Scott, Elizabeth J Cartwright, Gillian Hawcroft, Sarah L Perry, Nicola Ingram, Ian M Carr, Alexander F Markham, Constanze Bonifer, P Louise Coletta
Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the Apc (Min/+) mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas from cLys-Cox-2 x Apc (Min/+) mice was associated with significantly increased tumour size (P = 0...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729358/targeting-c-type-lectin-receptors-a-high-carbohydrate-diet-for-dendritic-cells-to-improve-cancer-vaccines
#17
REVIEW
Dieke van Dinther, Dorian A Stolk, Rieneke van de Ven, Yvette van Kooyk, Tanja D de Gruijl, Joke M M den Haan
There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729245/a-novel-mouse-model-of-radiation-induced-cancer-survivorship-diseases-of-the-gut
#18
Cecilia Magdalena Bull, Dilip Malipatlolla, Marie Kalm, Fei Sjöberg, Eleftheria Alevronta, Rita Grandér, Pedram Sultanian, Linda Persson, Martina Boström, Yohanna Eriksson, John Swanpalmer, Agnes E Wold, Klas Blomgren, Thomas Björk-Eriksson, Gunnar Steineck
A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative in order to prevent, alleviate or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses, while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1,5 cm of the colorectum using a linear accelerator...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#19
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28728298/-the-prognostic-analysis-of-hepatocellular-carcinoma-based-on-the-tumor-neo-vessels-macrophages-and-%C3%AE-sma-in-tumor-microenvironment
#20
M Fang, J P Yuan, L L Liu, G P Cheng, H J Ying, Y M Chen, M Chen
Objective: To analyze the quantitative expression and prognostic significance of tumor neo-vessels, macrophages and fibroblasts in tumor microenvironment of hepatocellular carcinoma (HCC). Methods: The clinic-pathological features and tissue samples for 101 HCC cases were collected. Immunohistochemistry was used to stain the tumor neo-vessels, macrophages and fibroblasts on tumor tissue. The distribution results and quantitative data of above key components were acquired by inverted microscopy equipped with CRi Nuance multispectral analysis system...
July 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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