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Tumor microenvironent

Tina Bernadette Angerer, Ylva Magnusson, Goran Landberg, John Stephen Fletcher
Breast cancer is an umbrella term used to describe a collection of different diseases with broad inter- and intra-tumor heterogeneity. Understanding this variation is critical in order to develop, and precisely prescribe, new treatments. Changes in the lipid metabolism of cancerous cells can provide important indications as to the metabolic state of the cells but are difficult to investigate with conventional histological methods. Due to the introduction of new higher energy (40 kV) gas cluster ion beams (GCIBs) time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is now capable of providing information on the distribution of hundreds of molecular species simultaneously on a cellular to sub-cellular scale...
October 26, 2016: Analytical Chemistry
Pedro Berraondo, Luna Minute, Daniel Ajona, Leticia Corrales, Ignacio Melero, Ruben Pio
Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors...
November 2016: Immunological Reviews
Yang Yu, Yan Liu, Chen Zong, Qingbo Yu, Xue Yang, Lei Liang, Fei Ye, Li Nong, Yuxian Jia, Yongkui Lu, Zhipeng Han
Mesenchymal stem cells (MSCs) are generally used in regenerative medicine, tissue engineering and therapy for immune disorder diseases. However, due to the immunosuppressive function of MSCs, the application of MSCs in breast cancer therapy remains limited. Sirt1 is the closest mammalian homologue of the yeast enzyme Sir2 which has an established capacity to influence yeast replicative lifespan. In this study, we demonstrated the effect of MSCs with Sirt1 overexpression (MSCs-Sirt1) in mice bearing 4T1 breast cancer and investigated the underlying mechanism...
October 26, 2016: Scientific Reports
Carrie S Shemanko, Yingying Cong, Amanda Forsyth
The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women...
October 22, 2016: International Journal of Molecular Sciences
Daniel Wai-Hung Ho, Regina Cheuk-Lam Lo, Lo-Kong Chan, Irene Oi-Lin Ng
The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis...
October 2016: Liver Cancer
Carl Neuerburg, Theresa Loer, Lena Mittlmeier, Christina Polan, Zsuzsanna Farkas, Lesca Miriam Holdt, Sandra Utzschneider, Jens Schwiesau, Thomas M Grupp, Wolfgang Böcker, Attila Aszodi, Christian Wedemeyer, Christian Kammerlander
Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO...
October 18, 2016: International Journal of Molecular Medicine
Massimo Alfano, Manuela Nebuloni, Raffaele Allevi, Pietro Zerbi, Erika Longhi, Roberta Lucianò, Irene Locatelli, Angela Pecoraro, Marco Indrieri, Chantal Speziali, Claudio Doglioni, Paolo Milani, Francesco Montorsi, Andrea Salonia
In the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation. We analyzed the 3D structure, geometrical measurements and anisotropy of the ECM isolated from (i) human bladder mucosa (basal lamina and lamina propria) and muscularis propria; and, (ii) bladder carcinoma (BC)...
October 25, 2016: Scientific Reports
Nikos A Afratis, Konstantina Karamanou, Zoi Piperigkou, Demitrios H Vynios, Achilleas D Theocharis
Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules...
October 24, 2016: Glycoconjugate Journal
Genevieve M Weir, Olga Hrytsenko, Tara Quinton, Neil L Berinstein, Marianne M Stanford, Marc Mansour
BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously...
2016: Journal for Immunotherapy of Cancer
Neha Kamran, Mayuri Chandran, Pedro R Lowenstein, Maria G Castro
Various preclinical studies have demonstrated that the success of immunotherapeutic strategies in inhibiting tumor progression in animal models of Glioblastoma multiforme (GBM). It is also evident that tumor-induced immune suppression drastically impacts the efficacy of immune based therapies. Among the mechanisms employed by GBM to induce immunosuppression is the accumulation of regulatory T cells (Tregs) and Myeloid derived suppressor cells (MDSCs). Advancing our understanding about the pathways regulating the expansion, accumulation and activity of MDSCs will allow for the development of therapies aimed at abolishing the inhibitory effect of these cells on immunotherapeutic approaches...
October 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Anais Fradet, Mathilde Bouchet, Carine Delliaux, Manon Gervais, Casina Kan, Claire Benetollo, Francesco Pantano, Geoffrey Vargas, Lamia Bouazza, Martine Croset, Yohann Bala, Xavier Leroy, Thomas J Rosol, Jennifer Rieusset, Akeila Bellahcène, Vincent Castronovo, Jane E Aubin, Philippe Clézardin, Martine Duterque-Coquillaud, Edith Bonnelye
Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro...
October 20, 2016: Oncotarget
Alexandre Chlenski, Marija Dobratic, Helen R Salwen, Mark Applebaum, Lisa J Guerrero, Ryan Miller, Gillian DeWane, Elena Solomaha, Jeremy D Marks, Susan L Cohn
SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation...
October 20, 2016: Oncotarget
Kuntal Kanti Goswami, Madhurima Sarkar, Sarbari Ghosh, Akata Saha, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Saptak Banerjee, Soumyabrata Roy, Anamika Bose, Parthasarathi Dasgupta, Rathindranath Baral
Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b(+)F4/80(high)) to M1 (CD11b(+)F4/80(low)) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1...
October 21, 2016: Molecular Immunology
Wei-Lin Jin, Xiao-Yuan Mao, Guan-Zhong Qiu
Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways...
October 24, 2016: Medicinal Research Reviews
Famke Aeffner, Nathan T Martin, Mirza Peljto, Joshua C Black, Justin K Major, Maryam Jangani, Michael O Ports, Joseph S Krueger, G David Young
Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from Kras(LSL-G12D/+); Trp53(LSL-R172H/+); Pdx-Cre (KPC) mice, a validated model of PDAC development...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Theresa L Whiteside
Tumor-derived exosomes (TEX) are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions...
October 20, 2016: Vaccines
Sara Crotti, Martina Piccoli, Flavio Rizzolio, Antonio Giordano, Donato Nitti, Marco Agostini
Colorectal cancer (CRC) whit more than a million of new cases per year is one of the most common registered cancers worldwide with few treatment options especially for advanced and metastatic patients. The tumor microenvironment is composed by extracellular matrix (ECM), cells and interstitial fluids. Among all these constituents, in the last years an increased interest around the ECM and its potential role in cancer tumorigenesis is arisen. During cancer progression the ECM structure and composition became disorganized, allowing cellular transformation and metastasis...
October 24, 2016: Journal of Cellular Physiology
Jia Sun, Jintang Sun, Bingfeng Song, Lin Zhang, Qianqian Shao, Yanguo Liu, Daoying Yuan, Yun Zhang, Xun Qu
In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4(+) T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22...
October 24, 2016: Scientific Reports
Anil K Deshantri, Sander A A Kooijmans, Sylvia A Kuijpers, Maria Coimbra, Astrid Hoeppener, Gert Storm, Marcel H A M Fens, Raymond M Schiffelers
Cancers are abundantly infiltrated by inflammatory cells that are modulated by tumor cells to secrete mediators fostering tumor cell survival and proliferation. Therefore, agents that interfere with inflammatory signaling molecules or specific immune cell populations have been investigated as anticancer drugs. Corticosteroids are highly potent anti-inflammatory drugs, whose activity is intensified when targeted by nanocarrier systems. Liposome-targeted corticosteroids have been shown to inhibit tumor growth in different syngeneic murine tumor models as well as human xenograft mouse models, which is attributed to a switch in the tumor microenvironment from a pro-inflammatory to an anti-inflammatory state...
October 20, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jong Chul Park, Noah M Hahn
Tremendous advances in our understanding of the tumor immunology and molecular biology of urothelial carcinoma (UC) have led to the recent approval of immunotherapy as a novel option for patients with UC with advanced disease. Despite the promising data of novel immune checkpoint inhibitors, only a small subset of patients with UC achieves durable remissions. Because an optimal antitumor response requires coordination of multiple immune, tumor, and microenvironment effector cells, novel approaches targeting distinct mechanisms of action likely in combination are needed...
October 20, 2016: Urologic Oncology
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