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Tumour microenvironment

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https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#1
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435394/the-role-of-mast-cells-in-oral-squamous-cell-carcinoma
#2
REVIEW
Swetha Gudiseva, Arvind Babu Rajendra Santosh, Raviteja Chitturi, Vamsikrishna Anumula, Chandrashekar Poosarla, Venkat Ramana Reddy Baddam
The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28433787/facile-encapsulation-of-hydroxycamptothecin-nanocrystals-into-zein-based-nanocomplexes-for-active-targeting-drug-delivery-and-cell-imaging
#3
Hongdi Wang, Wei Zhu, Yunna Huang, Zhixian Li, Yanbin Jiang, Qiuling Xie
Nano-drug delivery systems that integrate inorganic and organic or even bioactive components into a single nanoscale platform are playing a greatly important role in cancer treatment. Here, the fabrication of a versatile nanocarrier based on self-assembled structures of gold nanoparticles (AuNPs)-zein is reported, which displays high drug-loading efficiency for needle-shaped hydroxycamptothecin (HCPT) nanocrystals. The surface modification with folate-conjugated polydopamine (PFA) renders them stable and also facilitates their selective cellular internalization and enhancement of endocytosis...
April 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28430635/unsuccessful-mitosis-in-multicellular-tumour-spheroids
#4
Annie Molla, Morgane Couvet, Jean-Luc Coll
Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#5
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28427085/tumour-invasiveness-the-local-and-systemic-environment-and-the-basis-of-staging-systems-in-colorectal-cancer
#6
J H Park, H van Wyk, C S D Roxburgh, P G Horgan, J Edwards, D C McMillan
BACKGROUND: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. METHODS: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR)...
April 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28427047/co-activation-of-tgf%C3%AE-and-wnt-signalling-pathways-abrogates-emt-in-ovarian-cancer-cells
#7
Tulika Mitra, Sib Sankar Roy
BACKGROUND/AIMS: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy. METHODS: The expression of the different components of signalling events were analyzed by QPCR, Western blot, Immunofluorescence microscopy and flow cytometry...
March 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28424513/super-multiplex-vibrational-imaging
#8
Lu Wei, Zhixing Chen, Lixue Shi, Rong Long, Andrew V Anzalone, Luyuan Zhang, Fanghao Hu, Rafael Yuste, Virginia W Cornish, Wei Min
The ability to visualize directly a large number of distinct molecular species inside cells is increasingly essential for understanding complex systems and processes. Even though existing methods have successfully been used to explore structure-function relationships in nervous systems, to profile RNA in situ, to reveal the heterogeneity of tumour microenvironments and to study dynamic macromolecular assembly, it remains challenging to image many species with high selectivity and sensitivity under biological conditions...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28423692/the-relationship-between-members-of-the-canonical-nf-%C3%AE%C2%BAb-pathway-components-of-tumour-microenvironment-and-survival-in-patients-with-invasive-ductal-breast-cancer
#9
Lindsay Bennett, Elizabeth A Mallon, Paul G Horgan, Andrew Paul, Donald C McMillan, Joanne Edwards
The aim of the present study was to examine the relationship between tumour NF-κB activation, tumour microenvironment including local inflammatory response (LIR) and cancer-specific survival in patients with operable ductal breast cancer.Immunohistochemistry (tissue microarray of 376 patients) and western blotting (MCF7 and MDA-MB-231 breast cancer cells) was performed to assess expression of key members of the canonical NF-κB pathway (inhibitory kappa B kinase (IKKβ) and phosphorylated p65 Ser-536 (p-p65))...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422745/targeting-of-the-breast-cancer-microenvironment-with-a-potent-and-linkable-oxindole-based-antiangiogenic-small-molecule
#10
Orestis Argyros, Theodoros Karampelas, Aimilia Varela, Xenophon Asvos, Athanasios Papakyriakou, Adamantia Agalou, Dimitris Beis, Constantinos H Davos, Demosthenes Fokas, Constantin Tamvakopoulos
The clinical efficacy of antiangiogenic small molecules (e.g., sunitinib) in breast carcinoma has largely failed with substantial off-target toxicity. We rationally designed and evaluated preclinically a novel sunitinib analogue, SAP, with favourable pharmacological properties and the ability to be readily conjugated to a targeting peptide or antibody for active tumour targeting.SAP was evaluated in silico and in vitro in order to verify target engagement (e.g., VEGFR2). Pharmacokinetic and biodistribution parameters were determined in mice using LC-MS/MS...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#11
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28416797/unification-of-de-novo-and-acquired-ibrutinib-resistance-in-mantle-cell-lymphoma
#12
Xiaohong Zhao, Tint Lwin, Ariosto Silva, Bijal Shah, Jiangchuan Tao, Bin Fang, Liang Zhang, Kai Fu, Chengfeng Bi, Jiannong Li, Huijuan Jiang, Mark B Meads, Timothy Jacobson, Maria Silva, Allison Distler, Lancia Darville, Ling Zhang, Ying Han, Dmitri Rebatchouk, Maurizio Di Liberto, Lynn C Moscinski, John M Koomen, William S Dalton, Kenneth H Shain, Michael Wang, Eduardo Sotomayor, Jianguo Tao
The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28416796/lysyl-oxidase-drives-tumour-progression-by-trapping-egf-receptors-at-the-cell-surface
#13
HaoRan Tang, Leo Leung, Grazia Saturno, Amaya Viros, Duncan Smith, Gianpiero Di Leva, Eamonn Morrison, Dan Niculescu-Duvaz, Filipa Lopes, Louise Johnson, Nathalie Dhomen, Caroline Springer, Richard Marais
Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#14
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28410543/probing-the-prostate-tumour-microenvironment-ii-impact-of-hypoxia-on-a-cell-model-of-prostate-cancer-progression
#15
Claire Tonry, John Armstrong, Stephen Pennington
Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410380/interleukin-10-and-prostaglandin-e2-have-complementary-but-distinct-suppressive-effects-on-toll-like-receptor-mediated-dendritic-cell-activation-in-ovarian-carcinoma
#16
Eva Brencicova, Ann L Jagger, Hayley G Evans, Mirella Georgouli, Alex Laios, Steve Attard Montalto, Gautam Mehra, Jo Spencer, Ahmed A Ahmed, Shanti Raju-Kankipati, Leonie S Taams, Sandra S Diebold
Dendritic cells (DC) have the potential to instigate a tumour-specific immune response, but their ability to prime naïve lymphocytes depends on their activation status. Thus, for tumour immunotherapy to be effective, the provision of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is crucial in order to overcome immunosuppression associated with the tumour microenvironment. To address this, we investigated how ovarian carcinoma (OC)-associated ascites impedes activation of DC by TLR agonists...
2017: PloS One
https://www.readbyqxmd.com/read/28409855/the-mobility-of-mitochondria-intercellular-trafficking-in-health-and-disease
#17
Michael V Berridge, Jiri Neuzil
The view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells grow tumours only after acquiring mtDNA from cells in the local microenvironment resulting in respiration recovery, tumorigenesis and metastasis...
April 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28405689/differential-effects-of-sulforaphane-in-regulation-of-angiogenesis-in-a-co-culture-model-of-endothelial-cells-and-pericytes
#18
Yichong Wang, Zhigang Zhou, Wei Wang, Ming Liu, Yongping Bao
Aberrant neovascularization supports nutrients and the oxygen microenvironment in tumour growth, invasion and metastasis. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to possess chemopreventive properties. In the present study, the effects of SFN on cell proliferation and tubular formation have been investigated using endothelial cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on the growth of ECs and pericytes with IC50 values 46...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28404796/tuning-cancer-fate-the-unremitting-role-of-host-immunity
#19
REVIEW
B Calì, B Molon, A Viola
Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28401653/selective-blockade-of-b7-h3-enhances-antitumour-immune-activity-by-reducing-immature-myeloid-cells-in-head-and-neck-squamous-cell-carcinoma
#20
Liang Mao, Teng-Fei Fan, Lei Wu, Guang-Tao Yu, Wei-Wei Deng, Lei Chen, Lin-Lin Bu, Si-Rui Ma, Bing Liu, Yansong Bian, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa...
April 11, 2017: Journal of Cellular and Molecular Medicine
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