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https://www.readbyqxmd.com/read/28930982/development-of-a-human-preclinical-model-of-osteoclastogenesis-from-peripheral-blood-monocytes-co-cultured-with-breast-cancer-cell-lines
#1
Laura Mercatali, Chiara Spadazzi, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Federica Recine, Dino Amadori, Toni Ibrahim
The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We developed an in vitro fully human preclinical model of a co-culture of breast cancer cells and monocytes undergoing differentiation towards osteoclasts. We optimized a model of osteoclastogenesis starting from a sample of peripheral blood collected from healthy donors. Peripheral blood mononuclear cells (PBMCs) were first separated by density gradient centrifugation, seeded at a high density and induced to differentiate by adding two growth factors (GFs): receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF)...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930154/autophagy-and-inflammatory-response-in-the-tumor-microenvironment
#2
REVIEW
Daniel Ngabire, Gun-Do Kim
Cell death is the last fate of the life cycle of cells. Different pathways involved in cell death are known to date, and are mostly represented by apoptosis, necrosis, and autophagy. Autophagy is one of the most preserved cell death pathways, characterized by the elimination of large parts of cytoplasmic components after being consumed by a double-membraned vesicle called an autophagosome. The formed autophagosome then fuses with a lysosome containing degrading enzymes and leads to the digestion of the autophagosome content...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#3
REVIEW
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928836/preoperative-serum-macrophage-activated-biomarkers-soluble-mannose-receptor-smr-and-soluble-haemoglobin-scavenger-receptor-scd163-as-novel-markers-for-the-diagnosis-and-prognosis-of-gastric-cancer
#4
Dongbing Ding, Yang Song, Yao Yao, Songbai Zhang
Soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163) are macrophage activation markers which have previously been demonstrated to be increased in patients with inflammation, auto-immunity and malignancies. To investigate the clinical diagnostic and prognostic significance of preoperative serum sMR and sCD163, the present study investigated 143 gastric cancer (GC) patients, 66 subjects with benign gastric disease and 59 healthy controls, using an ELISA assay. Preoperative serum levels of sMR and sCD163 ranged from 0...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928657/colocynth-extracts-prevent-epithelial-to-mesenchymal-transition-and-stemness-of-breast-cancer-cells
#5
Kaushik Chowdhury, Ankit Sharma, Suresh Kumar, Gyanesh K Gunjan, Alo Nag, Chandi C Mandal
Modern treatment strategies provide better overall survival in cancer patients, primarily by controlling tumor growth. However, off-target and systemic toxicity, tumor recurrence, and resistance to therapy are still inadvertent hurdles in current treatment regimens. Similarly, metastasis is another deadly threat to patients suffering from cancer. This has created an urgent demand to come up with new drugs having anti-metastatic potential and minimum side effects. Thus, this study was aimed at exploring the anti-proliferative and anti-metastatic potential of colocynth medicinal plant...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928376/oligo-fucoidan-prevents-il-6-and-ccl2-production-and-cooperates-with-p53-to-suppress-atm-signaling-and-tumor-progression
#6
Li-Mei Chen, Po-Yen Liu, Yen-An Chen, Hong-Yu Tseng, Pei-Chun Shen, Pai-An Hwang, Hsin-Ling Hsu
Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53(+/+)) or without (p53(-/-)) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928161/the-immune-microenvironment-confers-chemoresistance-of-colorectal-cancer-through-macrophage-derived-il-6
#7
Zhaohui Huang, Yuan Yin, Surui Yao, Yaling Hu, Yuyang Feng, Min Li, Zehua Bian, Jiwei Zhang, Yan Qin, Xiaowei Qi, Le-Yuan Zhou, Bojian Fei, Jian Zou, Dong Hua
PURPOSE: Tumor-associated macrophages (TAMs) are frequently associated with poor prognosis in human cancers. However, the effects of TAM in colorectal cancer (CRC) are contradictory. We therefore investigated the functions, mechanisms and clinical significance of TAMs in CRC. EXPERIMENTAL DESIGN: We measured the macrophage infiltration (CD68), P-gp and Bcl2 expression in CRC tissues using Immunohistochemistry staining. Co-culture of TAMs and CRC cells both in vitro and in vivo models was used to evaluate the effects of TAMs on CRC chemoresistance...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928159/bmp4-induces-m2-macrophage-polarization-and-favors-tumor-progression-in-bladder-cancer
#8
Víctor G Martínez, Carolina Rubio, Mónica Martínez-Fernández, Cristina Segovia, Fernando López-Calderón, Marina Garín, Alicia Teijeira, Ester Munera-Maravilla, Alberto Varas, Rosa Sacedón, Felix Guerrero-Ramos, Felipe Villacampa, Federico de la Rosa, Daniel Castellano, Eduardo López-Collazo, Jesus M Paramio, Ángeles Vicente, Marta Dueñas
PURPOSE: Bladder cancer (BC) is a current clinical and social problem. At diagnosis, most patients present non-muscle invasive tumors, characterized by a high recurrence rate, which could progress to muscle invasive disease and metastasis. Bone morphogenetic protein (BMP)-dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in BC is still unclear. EXPERIMENTAL DESIGN: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927767/gem-dithioacetylated-indole-derivatives-as-novel-antileishmanial-agents
#9
Sharad Porwal, Suman Gupta, Prem M S Chauhan
In this communication we report a serendipitously discovered hybrid molecule 1, combining fragment of 3 (an in vivo active antileishmanial molecule) with H2S donor moiety (known for bimodal behavior of cytoprotection and apoptosis), as antileishmanial agent. Compound 1 suppresses 99.82% parasitemia of L. donovani infected macrophages at 12.5μg/ml without even deforming them (CC50>100μg/ml). This compound appears cytotoxic for intracellular amastigotes while cytoprotective to host macrophages. The concept can be utilized to develop high therapeutic index NCE (New Chemical Entities) for other macrophage mediated diseases like tuberculosis and cancer...
September 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927159/diagnostic-value-of-inflammatory-cell-infiltrates-tumor-stroma-percentage-and-disease-free-survival-in-patients-with-colorectal-cancer
#10
Katarzyna Jakubowska, Wojciech Kisielewski, Luiza Kańczuga-Koda, Mariusz Koda, Waldemar Famulski
The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC)...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#11
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28923858/anti-cd137-suppresses-tumor-growth-by-blocking-reverse-signaling-by-cd137-ligand
#12
Sang W Kang, Sang Chul Lee, So H Park, Juyang Kim, Hyeon H Kim, Hyeon-Woo Lee, Su-Kil Seo, Byoung S Kwon, Hong R Cho, Byungsuk Kwon
CD137 (4-1BB) is a T cell co-stimulatory molecule and agonstic CD137 antibodies are currently being evaluated in clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923419/tumor-associated-macrophages-are-strongly-related-to-vascular-invasion-non-luminal-subtypes-and-interval-breast-cancer
#13
Tor A Klingen, Ying Chen, Hans Aas, Elisabeth Wik, Lars A Akslen
Tumor associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163 positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163 positive macrophages were counted in the most active areas (hot-spots) and dichotomized as high (upper quartile) and low counts...
September 15, 2017: Human Pathology
https://www.readbyqxmd.com/read/28922567/determination-of-pd-l1-expression-in-effusions-from-mesothelioma-by-immuno-cytochemical-staining
#14
Mohammed S I Mansour, Tomas Seidal, Ulrich Mager, Amir Baigi, Katalin Dobra, Annika Dejmek
BACKGROUND: Malignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1). PD-L1 is up-regulated in cancer cells, and the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion, thus providing a target for antitumor therapy. Further, a correlation between PD-L1 expression and prognosis has been reported...
September 18, 2017: Cancer
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#15
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919995/mammary-tumor-derived-ccl2-enhances-pro-metastatic-systemic-inflammation-through-upregulation-of-il1%C3%AE-in-tumor-associated-macrophages
#16
Kelly Kersten, Seth B Coffelt, Marlous Hoogstraat, Niels J M Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W Doornebal, Cheei-Sing Hau, Max D Wellenstein, Camilla Salvagno, Parul Doshi, Esther H Lips, Lodewyk F A Wessels, Karin E de Visser
Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919508/pro-inflammatory-chitosan-poly-%C3%AE-glutamic-acid-nanoparticles-modulate-human-antigen-presenting-cells-phenotype-and-revert-their-pro-invasive-capacity
#17
Flávia Castro, Marta L Pinto, Andreia M Silva, Catarina L Pereira, Graciosa Q Teixeira, Maria Gomez-Lazaro, Susana G Santos, Mário A Barbosa, Raquel M Gonçalves, Maria J Oliveira
Anticancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals provided by antigen-presenting cells (APCs). However, it is described that immature dendritic cells (DCs) and macrophages at the tumor site may have an immunosuppressive profile, which limits the activity of effector T cells and supports tumor progression. Therapeutic targeting of these innate immune cells, either aiming at their elimination or re-polarization towards an immunostimulatory profile, has been pointed as an attractive approach to control tumor progression...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28915803/tartrate-resistant-acid-phosphatase-trap-acp5-promotes-metastasis-related-properties-via-tgf%C3%AE-2-t%C3%AE-r-and-cd44-in-mda-mb-231-breast-cancer-cells
#18
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28915576/hepatic-b-cell-leukemia-3-suppresses-chemically-induced-hepatocarcinogenesis-in-mice-through-altered-mapk-and-nf-%C3%AE%C2%BAb-activation
#19
Nadine Gehrke, Marcus A Wörns, Amrit Mann, Yvonne Huber, Nadine Hoevelmeyer, Thomas Longerich, Ari Waisman, Peter R Galle, Jörn M Schattenberg
The transcriptional nuclear factor kappa B (NF-κB)-coactivator B cell leukemia-3 (Bcl-3) is a molecular regulator of cell death and proliferation. Bcl-3 has been shown to be widely expressed in different cancer types including hepatocellular carcinoma (HCC). Its influence on hepatocarcinogenesis is still undetermined. To examine the role of Bcl-3 in hepatocarcinogenesis mice with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) were exposed to diethylnitrosamine (DEN) and phenobarbital (PB). Hepatic Bcl-3 overexpression attenuated DEN/PB-induced hepatocarcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914667/metabolic-regulation-of-macrophages-in-tumor-microenvironment
#20
Jaehong Kim, Jong-Sup Bae
PURPOSE OF REVIEW: Insight into the metabolic changes in cancer has become so important that cancer is regarded as a disease entity full of metabolic implications. We summarize the recent findings pertaining to cancer cell-derived metabolic changes that regulate the function of macrophages to favor cancer cell survival, and the reported approaches to reverse these changes. RECENT FINDINGS: Since the observation and dramatic revitalization of the Warburg effect, metabolic changes were thought to be confined in cancer cells...
September 13, 2017: Current Opinion in Hematology
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