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tumor micro environment

Li Li, Kejun Zhang, Conghua Lu, Qin Sun, Sanjun Zhao, Lin Jiao, Rui Han, Caiyu Lin, Jianxin Jiang, Min Zhao, Yong He
Migration of cancer cells leads to the invasion of distant organs by primary tumors. Further, endogenous electric fields (EFs) in the tumor microenvironment direct the migration of lung cancer cells by a process referred to as electrotaxis - although the precise mechanism remains unclear. Caveolin-1 (Cav-1) is a multifunctional scaffolding protein that is associated with directional cell migration and lung cancer invasion; however, its precise role in lung cancer electrotaxis is unknown. In the present study, we first detected outward electric currents on the tumor body surface in lung cancer xenografts using a highly-sensitive vibrating probe...
November 10, 2017: Oncotarget
Marjorie A Curet, Jyoti J Watters
Gliomas are rich in extracellular nucleotides that modulate glioma cell production of multiple cytokines including interleukin (IL)-6, which strongly contributes to glioma cell proliferation. However, little is known about how nucleotide signaling modulates microglial/macrophage (MG/MP) cytokine production in the context of gliomas, nor how MG/MP purinergic P2 receptor expression changes in the tumor micro-environment. We hypothesized that: (1) expression of key P2Y receptors will be augmented in glioma-derived MG/MP, and (2) selective activation of these receptors in vitro will regulate microglial production of IL-6 and glioma cell proliferation...
November 30, 2017: Journal of Neuro-oncology
Panagiotis F Christopoulos, Nikolaos I Vlachogiannis, Christiana T Vogkou, Michael Koutsilieris
Breast cancer (BrCa) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. Despite the development of novel therapeutic modalities, triple-negative breast cancer (TNBC) remains an incurable disease. Androgen receptor (AR) is widely expressed in BrCa and its role in the disease may differ depending on the molecular subtype and the stage. Interestingly, AR has been suggested as a potential target candidate in TNBC, while sex hormone levels may regulate the role of AR in BrCa subtypes...
December 2017: Anticancer Research
Phillip C Spinosa, Kathryn E Luker, Gary D Luker, Jennifer J Linderman
Chemokine CXCL12 gradients drive chemotaxis in a CXCR4-dependent mechanism and have been implicated in cancer metastasis. While CXCL12 gradients are typically studied in organized, defined environments, the tumor microenvironment is disorganized. In vivo, CXCL12 gradients depend on many factors: the number and arrangement of cells secreting and degrading CXCL12, isoform-dependent binding to the extracellular matrix, diffusion, and circadian fluctuations. We developed a computational model of the tumor microenvironment to simulate CXCL12 gradient dynamics in disorganized tissue...
2017: PloS One
Sarah Theiner, Stijn J M Van Malderen, Thibaut Van Acker, Anton Legin, Bernhard K Keppler, Frank Vanhaecke, Gunda Koellensperger
Multicellular tumor spheroid models serve as an important three-dimensional in vitro cell model system as they mimic the complex tumor microenvironment and thus have contributed to valuable assays in drug discovery studies. In this study, we present a state-of-the-art laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) setup for high spatial resolution elemental imaging of multicellular tumor spheroids and an approach to account for variations in cell density. A low dispersion LA-ICPMS setup was employed, providing accelerated throughput and high sensitivity and permitting a lateral image resolution down to ∼2...
November 15, 2017: Analytical Chemistry
Inderpal Singh, Gurvinder Singh, Vijeshwar Verma, Shashank Singh, Ratna Chandra
Many aggressive and metastatic cancer cell types show Warburg Effect; therefore, it is a possible adaptation helping cancer cells to rapidly divide and utilize the glycolytic intermediates for biosynthesis of ribose sugars (for nucleotide biosynthesis), fatty acid synthesis (lipids for membrane synthesis), NADPH (cellular currency for reductive biosynthesis) and lactate. This in due course results in decrease of extracellular pH, leading to acidic tumor micro-environment. EGFR is a crucial cell surface signaling receptor implicated in cancer cell survival and progression...
November 4, 2017: Interdisciplinary Sciences, Computational Life Sciences
C Rodrigo Pimentel, Suk Kyu Ko, Claudia Caviglia, Anders Wolff, Jenny Emnéus, Stephan Sylvest Keller, Martin Dufva
One of the fundamental steps needed to design functional tissues and, ultimately organs is the ability to fabricate thick and densely populated tissue constructs with controlled vasculature and microenvironment. To date, bioprinting methods have been employed to manufacture tissue constructs with open vasculature in a square-lattice geometry, where the majority lacks the ability to be directly perfused. Moreover, it appears to be difficult to fabricate vascular tissue constructs targeting the stiffness soft tissues such as the liver...
November 1, 2017: Acta Biomaterialia
Yunzhou Shi, Jason Oeh, Anna Hitz, Maj Hedehus, Jeffrey Eastham-Anderson, Franklin V Peale, Patricia Hamilton, Thomas O'Brien, Deepak Sampath, Richard A D Carano
The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment...
November 2017: Neoplasia: An International Journal for Oncology Research
Aman Sharma
Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator of cellular signaling, stem cell (both normal, and cancer stem cells) secreted exosome orchestrate various autocrine and paracrine functions which alter tumor micro-environment, growth and progression. Exosomes secreted by one of the two important stem cell phenotypes in cancers a) Mesenchymal stem cells, and b) Cancer stem cells not only promote cancerous growth but also impart therapy resistance in cancer cells...
October 6, 2017: International Journal of Cancer. Journal International du Cancer
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
September 22, 2017: Oncotarget
Olesja Hazenbiller, Saghar Nasr, Roman J Krawetz, Neil A Duncan
The use of embryonic stem cells (ESC) in regenerative medicine is restricted due to the possibility of tumorigenicity after inefficient or incomplete differentiation. Studies from our group, and others, suggest that mechanical stimuli may have a suppressive effect on the pluripotency/tumorigenesis of murine ESC (mESC). Furthermore, we have demonstrated that mESC seeded in a type I collagen scaffold, and transplanted into a murine bone fracture model, demonstrated repair without tumor formation. However, it remains unknown if mechanical factors were involved in blocking tumorigenicity of the mESC...
October 4, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Xiajing Fan, Hongru Liu, Miao Liu, Yuanyuan Wang, Li Qiu, Yanfen Cui
Rapid proliferation and Warburg effect make cancer cells consume plenty of glucose, which induces a low glucose micro-environment within the tumor. Up to date, how cancer cells keep proliferating in the condition of glucose insufficiency still remains to be explored. Recent studies have revealed a close correlation between excessive fructose consumption and breast cancer genesis and progression, but there is no convincing evidence showing that fructose could directly promote breast cancer development. Herein, we found that fructose, not amino acids, could functionally replace glucose to support proliferation of breast cancer cells...
2017: PeerJ
Lin Hua, Hong Xia, Wei-Ying Zheng, Li An
BACKGROUND: Transforming growth factor (TGF)-β is over-expressed in a wide variety of cancers such as lung adenocarcinoma. TGF-β plays a major role in cancer progression through regulating cancer cell proliferation and remodeling of the tumor micro-environment. However, it is still a great challenge to explain the phenotypic effects caused by TGF-β stimulation and the effect of TGF-β stimulation on tumor micro-environment. OBJECTIVES: To address this issue, in the present study we used two time-course microarray data in human lung adenocarcinoma cells and applied bioinformatics methods to explore the gene regulation network responding to TGF-β stimulation in lung adenocarcinoma cells...
March 2017: Iranian Journal of Biotechnology
Ioannis A Voutsadakis
   The immune system has come to the forefront of cancer therapeutics in recent years with the success of immune blockade inhibitors in a variety of cancers whose list is increasing with a quick pace. Despite the efficacy of these drugs across a significant part of the cancer spectrum, responses are still seen only in a minority of patients, that implies that most patients are refractory or promptly develop resistance to these agents. Mechanisms of this resistance are important to decipher as this knowledge may lead to the introduction of additional therapies or manipulations to modulate resistance...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
D C M Pereira-Fonseca, F M Oliveira-Rovai, L A C Rodas, C A C Beloti, R B P Torrecilha, P K R K Ito, S V Avanço, R S Cipriano, Y T Utsunomiya, R M Hiramoto, L Calvo-Bado, O Courtenay, G F Machado, V M F Lima, C M Nunes
Visceral leishmaniosis is a zoonotic disease that is transmitted by Lutzomyia longipalpis sandflies. Dogs are the main peri-urban reservoir of the disease, and progression of canine leishmaniosis is dependent on the type of immune response elaborated against the parasite. Type 1 immunity is characterized by effective cellular response, with production of pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). In contrast, Type 2 immunity is predominantly humoral, associated with progression of the disease and mediated by anti-inflammatory cytokines such as interleukin 10 (IL-10)...
November 2017: Parasite Immunology
Yongchang Lai, Liang Tao, Yifan Zhao, Xiaomin Zhang, Xingjuan Sun, Qin Wang, Chengfang Xu
Tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand (TRAIL) can trigger the extrinsic apoptosis pathway. Our previous study indicated that connexin32 (Cx32) inhibited streptonigrin-induced intrinsic apoptosis via the epidermal growth factor receptor (EGFR) pathway. However, whether Cx32 can exert effects on the extrinsic apoptosis pathway through EGFR signaling remains unclear. In the present study, we investigated the role of Cx32 in extrinsic apoptosis induced by treatment with TNFα + cycloheximide (CHX) or afatinib in human cervical cancer (CaCx) cells...
November 2017: Oncology Reports
Hua Du, Jing Zhao, Ling Hai, Jing Wu, Hua Yi, Yonghong Shi
Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues...
September 8, 2017: Cancer Biology & Therapy
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
August 8, 2017: Oncotarget
A Y Efremenko, J L Campbell, D E Dodd, A R Oller, H J Clewell
While insoluble nickel subsulfide (Ni3 S2 ) was carcinogenic in the lung in a 2-year rat bioassay, soluble nickel sulfate hexahydrate (NiSO4* 6H2 O) was not. To investigate whether differences in the cellular responses to these two nickel compounds could underlie their differential activities, we conducted parallel studies to determine the gene expression changes in micro-dissected lung distal airway cells from Fischer 344 rats following inhalation of the two compounds for one and four weeks (6 hr per day, 5 days per week)...
October 2017: Environmental and Molecular Mutagenesis
Mohammad Hossein Zangooei, Jafar Habibi
BACKGROUND: Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. METHODS: In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods...
2017: PloS One
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