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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/28722681/the-role-of-toll-like-receptor-4-in-tumor-microenvironment
#1
REVIEW
Jing Li, Fan Yang, Feng Wei, Xiubao Ren
Tumors are closely related to chronic inflammation, during which there are various changes in inflammatory sites, such as immune cells infiltration, pro-inflammation cytokines production, and interaction between immune cells and tissue cells. Besides, substances, released from both tissue cells attacked by exogenous etiologies, also act on local cells. These changes induce a dynamic and complex microenvironment favorable for tumor growth, invasion, and metastasis. The toll-like receptor 4 (TLR4) is the first identified member of the toll-like receptor family that can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMPs)...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#2
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28708600/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#3
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707078/ctla-4-expression-in-the-non-small-cell-lung-cancer-patient-tumor-microenvironment-diverging-prognostic-impact-in-primary-tumors-and-lymph-node-metastases
#4
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee, Elin Richardsen, Sigurd M Hald, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes...
July 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28705007/pancreas-adenocarcinoma-novel-therapeutics
#5
Benjamin A Krantz, Kenneth H Yu, Eileen M O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is the third highest cause of cancer-related deaths in the US, and is projected to be second only to non-small cell lung cancer (NSCLC) by the 2020s. Current therapies have a modest impact on survival and median overall survival (mOS) across all stages of disease remains under a year. Over the last decade, however, great strides have been made in the understanding of PDAC pathobiology including the role of the tumor microenvironment (TME), DNA damage repair and mechanism of immunosuppression...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28694739/chemotherapy-and-tumor-microenvironment-of-pancreatic-cancer
#6
REVIEW
Qiaofei Liu, Quan Liao, Yupei Zhao
Pancreatic cancer is an extremely dismal malignance. Chemotherapy has been widely applied to treat this intractable tumor. It has exclusive tumor microenvironment (TME), characterized by dense desmoplasia and profound infiltrations of immunosuppressive cells. Interactions between stromal cells and cancer cells play vital roles to affect the biological behaviors of pancreatic cancer. Targeting the stromal components of pancreatic cancer has shown promising results. In addition to the direct toxic effects of chemotherapeutic drugs on cancer cells, they can also remodel the TME, eventually affecting their efficacy...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28693897/connexins-important-players-in-the-dissemination-of-prostate-cancer-cells
#7
REVIEW
Jonathan Boucher, Arnaud Monvoisin, Justine Vix, Marc Mesnil, Dominique Thuringer, Françoise Debiais, Laurent Cronier
Over the past 50 years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoral profile for most of invasion and dissemination steps to secondary sites...
July 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28691356/tumor-microenvironment-and-noncoding-rnas-as-co-drivers-of-epithelial-mesenchymal-transition-and-cancer-metastasis
#8
REVIEW
Kinan Drak Alsibai, Didier Meseure
Reciprocal interactions between cancer cells and tumor microenvironment (TME) are crucial events in tumor progression and metastasis. Pervasive stromal reprogramming of TME modifies numerous cellular functions including, extracellular matrix (ECM) stiffness, inflammation and immunity. These environmental factors allow selection of more aggressive cells that develop adaptive strategies associating plasticity and epithelial-mesenchymal transition (EMT), stem-like phenotype, invasion, immunosuppression, and resistance to therapies...
July 10, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28690108/improving-homing-in-t-cell-therapy
#9
Debora Vignali, Marinos Kallikourdis
Cytotoxic T lymphocytes (cytotoxic T cells, CTLs) are an immune effector cell population that can mediate specific immune responses against cancer. Based on this concept, tumor immunotherapy protocols have been developed using adoptive transfer of in vitro-expanded autologous T cells that can kill cancer cells. However, fully functional adoptive T cell therapies (ACT) are hampered by the inability to guarantee that all transferred T cells manage to reach the tumor sites and make contact with cancer cells. The lack of tumor homing of T cells may be caused by a variety of reasons...
June 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28687621/cancer-associated-fibroblasts-share-characteristics-and-pro-tumorigenic-activity-with-mesenchymal-stromal-cells
#10
Lucia Borriello, Rie Nakata, Michael A Sheard, G Esteban Fernandez, Richard Sposto, Jemily Malvar, Laurence Blavier, Hiroyuki Shimada, Shahab Asgharzadeh, Robert C Seeger, Yves A DeClerck
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship to MSC is not clear. Here we have isolated from primary human neuroblastoma (NB) tumors a population of αFAP- and FSP-1-expressing CAF that share phenotypic and functional characteristics with bone marrow-derived MSC (BM-MSC). Analysis of human NB tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28683102/identification-of-prognostic-collagen-signatures-and-potential-therapeutic-stromal-targets-in-canine-mammary-gland-carcinoma
#11
Ashley Case, Becky K Brisson, Amy C Durham, Suzanne Rosen, James Monslow, Elizabeth Buza, Pascale Salah, Julie Gillem, Gordon Ruthel, Sridhar Veluvolu, Veronica Kristiansen, Ellen Puré, Dorothy C Brown, Karin U Sørenmo, Susan W Volk
Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28681373/the-role-of-tumor-associated-macrophage-in-breast-cancer-biology
#12
REVIEW
Junjeong Choi, Jones Gyamfi, Haerin Jang, Ja Seung Koo
Breast cancer is the most commonly diagnosed malignant tumor in women worldwide and contributes significantly as the primary cause of female cancer related mortality. Hence, research is focused on discovering new and effective treatment targets. The breast tumor microenvironment (TME) comprising of recruited host stromal cells and tumor cells, has recently emerged as an important player in tumor progression, with the potential for future treatment. The TME comprises immune system elements (such as macrophages and lymphocytes), cells composing blood vessel, fibroblast, myofibroblast, mesenchymal stem cells, adipocytes and extracellular matrix (ECM)...
July 6, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28680763/the-influence-of-stromal-cells-and-tumor-microenvironment-derived-cytokines-and-chemokines-on-cd3-cd8-tumor-infiltrating-lymphocyte-subpopulations
#13
Stefan Koeck, Johan Kern, Marit Zwierzina, Gabriele Gamerith, Edith Lorenz, Sieghart Sopper, Heinz Zwierzina, Arno Amann
The tumor microenvironment has been identified as a major mediator of immunological processes in solid tumors. In particular, tumor-associated fibroblasts are known to interact with tumor infiltrating immune cells. We describe the influence of fibroblasts and tumor-microenvironment-derived cytokines on the infiltration capacity of CD3(+)CD8(+) cytotoxic T lymphocyte subpopulations using a multicellular 3D co-culture system. 3D tumor microtissues were cultivated using a hanging drop system. Human A549 and Calu-6 cancer cell lines were incubated alone or together with the human fibroblast cell line SV80 for 10 d to form microtissues...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679779/molecular-effects-of-stromal-selective-targeting-by-upar-retargeted-oncolytic-virus-in-breast-cancer
#14
Yuqi Jing, Valery Chavez, Yuguang Ban, Nicolas Acquavella, Dorraya El-Ashry, Alexey Pronin, Xi Chen, Jaime R Merchan
The tumor microenvironment (TME) is a relevant target for novel biological therapies. MV-m-uPA and MV-h-uPA are fully retargeted, species-specific, oncolytic measles viruses (MVs) directed against murine or human urokinase receptor (PLAUR/uPAR), expressed in tumor and stromal cells. The effects of stromal selective targeting by uPAR retargeted MVs were investigated. In vitro infection, virus-induced GFP expression and cytotoxicity by MV-h-uPA and MV-m-uPA were demonstrated in human and murine cancer cells and cancer associated fibroblasts (CAFs) in a species-specific manner...
July 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28672102/prognostic-and-functional-role-of-subtype-specific-tumor-stroma-interaction-in-breast-cancer
#15
Giuseppe Merlino, Patrizia Miodini, Maurizio Callari, Francesca D'Aiuto, Vera Cappelletti, Maria Grazia Daidone
None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs)...
July 3, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28670477/ex-vivo-tumor-culture-systems-for-functional-drug-testing-and-therapy-response-prediction
#16
REVIEW
Titia G Meijer, Kishan At Naipal, Agnes Jager, Dik C van Gent
Optimal patient stratification is of utmost importance in the era of personalized medicine. Prediction of individual treatment responses by functional ex vivo assays requires model systems derived from viable tumor samples, which should closely resemble in vivo tumor characteristics and microenvironment. This review discusses a broad spectrum of model systems, ranging from classic 2D monolayer culture techniques to more experimental 'cancer-on-chip' procedures. We mainly focus on organotypic tumor slices that take tumor heterogeneity and tumor-stromal interactions into account...
June 2017: Future Science OA
https://www.readbyqxmd.com/read/28668832/imaging-the-role-of-multinucleate-pancreatic-cancer-cells-and-cancer-associated-fibroblasts-in-peritoneal-metastasis-in-mouse-models
#17
Kosuke Hasegawa, Atsushi Suetsugu, Miki Nakamura, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
BACKGROUND/AIM: The interaction between pancreatic-cancer cells and stromal cells in the tumor microenvironment (TME) is of particular importance in cancer progression and metastasis. The present report demonstrates the role of cancer-associated fibroblasts (CAFs) and multinucleate pancreatic-cancer cells in peritoneal metastasis. MATERIALS AND METHODS: An orthotopic mouse model of pancreatic cancer was established with the human pancreatic cancer cell line BxPC3, which stably expresses green fluorescent protein (GFP)...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28662235/use-of-pd-1-targeting-macrophage-infiltration-and-ido-pathway-activation-in-sarcomas-a-phase-2-clinical-trial
#18
Maud Toulmonde, Nicolas Penel, Julien Adam, Christine Chevreau, Jean-Yves Blay, Axel Le Cesne, Emmanuelle Bompas, Sophie Piperno-Neumann, Sophie Cousin, Thomas Grellety, Thomas Ryckewaert, Alban Bessede, François Ghiringhelli, Marina Pulido, Antoine Italiano
Importance: There is a strong rationale for treating sarcomas with immunotherapy. Objective: To assess the efficacy and safety of programmed cell death protein 1 (PD-1) targeting in combination with metronomic chemotherapy in sarcomas. Design, Setting, and Participants: This was an open-label, multicenter, phase 2 study of 4 cohorts of patients with advanced soft-tissue sarcoma (STS), including leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), other sarcomas (others), and gastrointestinal stromal tumor (GIST)...
June 29, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28656348/pap-reg3a-favors-perineural-invasion-in-pancreatic-adenocarcinoma-and-serves-as-a-prognostic-marker
#19
Jérémy Nigri, Meritxell Gironella, Christian Bressy, Elena Vila-Navarro, Julie Roques, Sophie Lac, Caroline Bontemps, Coraline Kozaczyk, Jérôme Cros, Daniel Pietrasz, Raphaël Maréchal, Jean-Luc Van Laethem, Juan Iovanna, Jean-Baptiste Bachet, Emma Folch-Puy, Richard Tomasini
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer...
June 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28653899/mutation-promoting-molecular-networks-of-uncontrolled-inflammation
#20
Hui Zhang, Xuanfu Xu
More and more studies show that chronic inflammation can lead to tumor formation. The complex interactions of inflammatory cells, stroma and tumor parenchymal cell are closely related to tumor formation. Under the state of chronic inflammatory microenvironment, long-term interaction of inflammatory cells and stromal cells as well as the parenchymal cells makes signaling pathway in parenchyma cells disordered. A series of gene level editor modification, epigenetic changes, and the regulation of transcription and translation changes will happen based on signaling pathway disorder...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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