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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28218738/adipogenic-niches-for-melanoma-cell-colonization-and-growth-in-bone-marrow
#1
Juan Wang, Guang-Liang Chen, Shan Cao, Ming-Chun Zhao, Yong-Qing Liu, Xiao-Xiang Chen, Cheng Qian
Bone marrow (BM) adipocytes are abundant in BM and may be involved in the process of bone metastasis. However, their behaviors in metastatic BM niches during bone metastasis have not been fully explored. In this study, intracardiac transplantation of B16-F10 melanoma cells into immunocompetent C57BL/6 mice was performed. Tibial marrow sections were stained with hematoxylin and eosin, Masson's trichrome, tartrate-resistant acid phosphatase, and fatty acid-binding protein 4 (FABP4) and analyzed using a histomorphometric system...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28217128/tumor-associated-lymphatic-vessels-upregulate-pdl1-to-inhibit-t-cell-activation
#2
Lothar C Dieterich, Kristian Ikenberg, Timur Cetintas, Kübra Kapaklikaya, Cornelia Hutmacher, Michael Detmar
Tumor-associated lymphatic vessels (LVs) play multiple roles during tumor progression, including promotion of metastasis and regulation of antitumor immune responses by delivering antigen from the tumor bed to draining lymph nodes (LNs). Under steady-state conditions, LN resident lymphatic endothelial cells (LECs) have been found to maintain peripheral tolerance by directly inhibiting autoreactive T-cells. Similarly, tumor-associated lymphatic endothelium has been suggested to reduce antitumor T-cell responses, but the mechanisms that mediate this effect have not been clarified...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28211481/effects-of-strength-training-on-osteogenic-differentiation-and-bone-strength-in-aging-female-wistar-rats
#3
Monique Patricio Singulani, Camila Tami Stringhetta-Garcia, Leandro Figueiredo Santos, Samuel Rodrigues Lourenço Morais, Mário Jefferson Quirino Louzada, Sandra Helena Penha Oliveira, Antonio Hernandes Chaves Neto, Rita Cássia Menegati Dornelles
The effects of strength training (ST) on the mechanical bone strength and osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) from adult, aged and exercised aged rats were determined. The exercised aged animals displayed higher values of areal bone mineral density, compression test, alkaline phosphatase activity (ALP) and biological mineralization, while oil red O staining for adipocytes was lower. ST increased gene expression of runt-related transcription factor 2 (Runx2), osterix (Osx) as well as bone matrix protein expression, and reduced expression of peroxisome proliferator-activated receptor gamma (Pparγ)...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209609/pancreatic-cancer-progress-and-challenges-in-a-rapidly-moving-field
#4
Eric A Collisson, Kenneth P Olive
"Pancreatic Cancer: Advances in Science and Clinical Care," a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28206814/biomarkers-in-tumor-microenvironment-upregulation-of-fibroblast-activation-protein-%C3%AE-correlates-with-gastric-cancer-progression-and-poor-prognosis
#5
Mengmou Hu, Chengjia Qian, Ziwei Hu, Bojian Fei, Haibo Zhou
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28202677/cancer-associated-fibroblasts-modulate-growth-factor-signaling-and-extracellular-matrix-remodeling-to-regulate-tumor-metastasis
#6
REVIEW
Begum Erdogan, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the surrounding stroma of carcinomas that emerge in the tumor microenvironment as a result of signals derived from the cancer cells. Biochemical cross-talk between cancer cells and CAFs as well as mechanical remodeling of the stromal extracellular matrix (ECM) by CAFs are important contributors to tumor cell migration and invasion, which are critical for cancer progression from a primary tumor to metastatic disease. In this review, we discuss key paracrine signaling pathways between CAFs and cancer cells that promote cancer cell migration and invasion...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202510/myc-mediates-large-oncosome-induced-fibroblast-reprogramming-in-prostate-cancer
#7
Valentina R Minciacchi, Cristiana Spinelli, Mariana Reis-Sobreiro, Lorenzo Cavallini, Sungyong You, Mandana Zandian, Xiaohong Li, Paola Chiarugi, Rosalyn M Adam, Edwin M Posadas, Giuseppe Viglietto, Michael R Freeman, Emanuele Cocucci, Neil A Bhowmick, Dolores Di Vizio
Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#8
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197395/characterization-of-the-tumor-microenvironment-and-tumor-stroma-interaction-by-non-invasive-preclinical-imaging
#9
REVIEW
Nirilanto Ramamonjisoa, Ellen Ackerstaff
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28197361/nkp30-isoforms-and-nkp30-ligands-are-predictive-biomarkers-of-response-to-imatinib-mesylate-in-metastatic-gist-patients
#10
Sylvie Rusakiewicz, Aurélie Perier, Michaela Semeraro, Jonathan M Pitt, Elke Pogge von Strandmann, Katrin S Reiners, Sandrine Aspeslagh, Christelle Pipéroglou, Frédéric Vély, Alexandre Ivagnes, Sarah Jegou, Niels Halama, Loic Chaigneau, Pierre Validire, Christos Christidis, Thierry Perniceni, Bruno Landi, Anne Berger, Nicolas Isambert, Julien Domont, Sylvie Bonvalot, Philippe Terrier, Julien Adam, Jean-Michel Coindre, Jean-François Emile, Vichnou Poirier-Colame, Kariman Chaba, Benedita Rocha, Anne Caignard, Antoine Toubert, David Enot, Joachim Koch, Aurélien Marabelle, Marion Lambert, Sophie Caillat-Zucman, Serge Leyvraz, Christian Auclair, Eric Vivier, Alexander Eggermont, Christophe Borg, Jean-Yves Blay, Axel Le Cesne, Olivier Mir, Laurence Zitvogel
Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#11
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28187434/interface-between-breast-cancer-cells-and-the-tumor-microenvironment-using-platelet-rich-plasma-to-promote-tumor-angiogenesis-influence-of-platelets-and-fibrin-bundles-on-the-behavior-of-breast-tumor-cells
#12
Sheila Siqueira Andrade, Joana Tomomi Sumikawa, Eloísa Dognani Castro, Fabricio Pereira Batista, Edgar Paredes-Gamero, Lilian Carolina Oliveira, Izabel Monastério Guerra, Giovani Bravin Peres, Renan Pelluzzi Cavalheiro, Luiz Juliano, Afonso Pinto Nazário, Gil Facina, Siu Mui Tsai, Maria Luiza Vilela Oliva, Manoel João Batista Castello Girão
Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186976/32-phosphorus-selectively-delivered-by-listeria-to-pancreatic-cancer-demonstrates-a-strong-therapeutic-effect
#13
Dinesh Chandra, Benson Chellakkan Selvanesan, Ziqiang Yuan, Steven K Libutti, Wade Koba, Amanda Beck, Kun Zhu, Arturo Casadevall, Ekaterina Dadachova, Claudia Gravekamp
Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186964/il-6-secreted-by-cancer-associated-fibroblasts-promotes-epithelial-mesenchymal-transition-and-metastasis-of-gastric-cancer-via-jak2-stat3-signaling-pathway
#14
Xiongyan Wu, Pan Tao, Quan Zhou, Jie Li, Zhenjia Yu, Xiaofeng Wang, Jiaanfang Li, Chen Li, Min Yan, Zhenggang Zhu, Bingya Liu, Liping Su
Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Here, we show that CAFs isolated from gastric cancer produce significant amounts of interleukin-6 (IL-6). CAFs enhances the migration and EMT of gastric cancer cells through the secretion of IL-6 that activates Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in gastric cancer cells, while deprivation of IL-6 using a neutralizing antibody or inhibition of JAK/STAT3 pathway with specific inhibitor AG490 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185288/metformin-effects-on-head-and-neck-squamous-carcinoma-microenvironment-window-of-opportunity-trial
#15
Joseph Curry, Jennifer Johnson, Patrick Tassone, Marina Domingo Vidal, Diana Whitaker Menezes, John Sprandio, Mehri Mollaee, Paolo Cotzia, Ruth Birbe, Zhao Lin, Kurren Gill, Elizabeth Duddy, Tingting Zhan, Benjamin Leiby, Michelle Reyzer, David Cognetti, Adam Luginbuhl, Madalina Tuluc, Ubaldo Martinez-Outschoorn
OBJECTIVE: The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY DESIGN: Window of opportunity trial of metformin between diagnostic biopsy and resection...
February 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28182873/biomechanically-primed-liver-microtumor-array-as-a-high-throughput-mechanopharmacological-screening-platform-for-stroma-reprogrammed-combinatorial-therapy
#16
Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types...
January 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28176627/a-review-of-ruthenium-complexes-activities-on-different-steps-of-the-metastatic-process-in-breast-cancer-cells
#17
Cecília Patrícia Popolin, Márcia Regina Cominetti
Cancer is one of the main causes of death worldwide. Breast cancer is the most prevalent type of cancer in women and the leading cause of cancer deaths due to its high metastasis to the lymph nodes, lungs bones and brain. Interactions with the stromal microenvironment surrounding tumor cells facilitate tumor cell migration and invasion of tissues and dissemination to other organs, to form metastasis. The development of antitumor metal-based drugs was originated with the discovery of cisplatin, however, its severe side effects represent a limitation for its clinical use...
6, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28174207/heparin-binding-epidermal-growth-factor-like-growth-factor-promotes-neuroblastoma-differentiation
#18
Angela L Gaviglio, Erik H Knelson, Gerard C Blobe
High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low Schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival...
February 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28173772/potential-importance-of-protease-activated-receptor-par-1-expression-in-the-tumor-stroma-of-non-small-cell-lung-cancer
#19
Cong Lin, Christof J Majoor, Joris J T H Roelofs, Martijn D de Kruif, Hugo M Horlings, Keren Borensztajn, C Arnold Spek
BACKGROUND: Protease activated receptor (PAR)-1 expression is increased in a variety of tumor cells. In preclinical models, tumor cell PAR-1 appeared to be involved in the regulation of lung tumor growth and metastasis; however the role of PAR-1 in the lung tumor microenvironment, which is emerging as a key compartment in driving cancer progression, remained to be explored. METHODS: In the present study, PAR-1 gene expression was determined in lung tissue from patients with non-small-cell lung cancer (NSCLC) using a combination of publicly available RNA microarray datasets and in house-made tissue microarrays including tumor biopsies of 94 patients with NSCLC (40 cases of adenocarcinoma, 42 cases of squamous cell carcinoma and 12 cases of other type of NSCLC at different stages)...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28166193/a-loop-of-cancer-stroma-cancer-interaction-promotes-peritoneal-metastasis-of-ovarian-cancer-via-tnf%C3%AE-tgf%C3%AE-egfr
#20
T-S Lau, L K-Y Chan, E C-H Wong, C W-C Hui, K Sneddon, T-H Cheung, S-F Yim, J H-S Lee, C S-Y Yeung, T K-H Chung, J Kwong
Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling...
February 6, 2017: Oncogene
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