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Tumour microenvironment

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https://www.readbyqxmd.com/read/28549626/cell-biology-metabolic-crosstalk-in-glioma
#1
REVIEW
Alison Colquhoun
The renewed interest in cancer metabolism in recent years has been fuelled by the identification of the involvement of key oncogenes and tumour suppressor genes in the control of metabolic pathways. Many of these alterations lead to dramatic changes in bioenergetics, biosynthesis and redox balance within tumour cells. The complex relationship between tumour cell metabolism and the tumour microenvironment has turned this field of biochemistry and cell biology into a challenging and exciting area for study. In the case of gliomas the involvement of altered metabolic pathways including glycolysis, oxidative phosphorylation and glutaminolysis are pointing the way to new possibilities for treatment...
May 23, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28548102/replicating-viral-vector-platform-exploits-alarmin-signals-for-potent-cd8-t-cell-mediated-tumour-immunotherapy
#2
Sandra M Kallert, Stephanie Darbre, Weldy V Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A Luther, Alfred Zippelius, Doron Merkler, Daniel D Pinschewer
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL(eff)) responses. Conversely, the induction of protective tumour-specific CTL(eff) and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28544640/an-in%C3%A2-vitro-model-demonstrates-the-potential-of-neoplastic-human-germ-cells-to-influence-the-tumour-microenvironment
#3
B Klein, H-C Schuppe, M Bergmann, M P Hedger, B E Loveland, K L Loveland
Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT...
May 23, 2017: Andrology
https://www.readbyqxmd.com/read/28541315/therapeutic-t-cell-engineering
#4
Michel Sadelain, Isabelle Rivière, Stanley Riddell
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28536438/optimizing-radiotherapy-protocols-using-computer-automata-to-model-tumour-cell-death-as-a-function-of-oxygen-diffusion-processes
#5
Perrine Paul-Gilloteaux, Vincent Potiron, Grégory Delpon, Stéphane Supiot, Sophie Chiavassa, François Paris, Sylvain V Costes
The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536346/taking-a-stab-at-cancer-oncolytic-virus-mediated-anti-cancer-vaccination-strategies
#6
REVIEW
Amelia Sadie Aitken, Dominic Guy Roy, Marie-Claude Bourgeois-Daigneault
Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28534531/unravelling-the-biology-of-sclc-implications-for-therapy
#7
REVIEW
Joshua K Sabari, Benjamin H Lok, James H Laird, John T Poirier, Charles M Rudin
Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints...
May 23, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28531108/regulation-of-metabolic-activity-by-p53
#8
REVIEW
Jessica Flöter, Irem Kaymak, Almut Schulze
Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction...
May 20, 2017: Metabolites
https://www.readbyqxmd.com/read/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#9
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28523716/cd44-fibroblasts-increases-breast-cancer-cell-survival-and-drug-resistance-via-igf2bp3-cd44-igf2-signalling
#10
Yonglei Liu, Conghui Yu, Yonggang Wu, Xiangjun Sun, Quanping Su, Cuiping You, Hongwu Xin
CD44, a cell adhesion protein, involves in various process in cancer such as cell survival and metastasis. Most researches on CD44 in cancer focus on cancer cells. Recently, it is found that CD44 expression is high in fibroblasts of tumour microenvironment. However, its role in communication between fibroblasts and breast cancer cells is seldom known. In this study, CD44-positive (CD44(+) Fbs) and CD44-negative carcinoma-associated fibroblasts (CD44(-) Fbs) were isolated and cocultured with breast cancer cells for analysis of cell survival and drug resistance...
May 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28516983/nanoparticle-design-strategies-for-enhanced-anticancer-therapy-by-exploiting-the-tumour-microenvironment
#11
REVIEW
Yunlu Dai, Can Xu, Xiaolian Sun, Xiaoyuan Chen
Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites. Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, hypoxia and acidic pH. There are many types of cells, including tumour cells, macrophages, immune and fibroblast cells, fed by defective blood vessels in the solid tumour. Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness. In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones...
May 18, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28515673/growth-of-mcf-7-breast-cancer-cells-and-efficacy-of-anti-angiogenic-agents-in-a-hydroxyethyl-chitosan-glycidyl-methacrylate-hydrogel
#12
Hejing Wang, Junmin Qian, Yaping Zhang, Weijun Xu, Juxiang Xiao, Aili Suo
BACKGROUND: Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28511092/epigenetics-and-immunotherapy-the-current-state-of-play
#13
REVIEW
Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#14
T Kryza, L M Silva, N Bock, R A Fuhrman-Luck, C R Stephens, J Gao, H Samaratunga, M G Lawrence, J D Hooper, Y Dong, G P Risbridger, J A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intra-epithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface...
May 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28508153/cellular-and-molecular-perspectives-in-rheumatoid-arthritis
#15
REVIEW
Douglas J Veale, Carl Orr, Ursula Fearon
Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA...
May 15, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28507714/targeting-the-tumour-microenvironment-with-an-enzyme-responsive-drug-delivery-system-for-the-efficient-therapy-of-breast-and-pancreatic-cancers
#16
Brigitte Renoux, Florian Raes, Thibaut Legigan, Elodie Péraudeau, Balkis Eddhif, Pauline Poinot, Isabelle Tranoy-Opalinski, Jérôme Alsarraf, Oleksandr Koniev, Sergii Kolodych, Stéphanie Lerondel, Alain Le Pape, Jonathan Clarhaut, Sébastien Papot
The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28504837/immunotherapy-for-metastatic-renal-cell-carcinoma
#17
REVIEW
Susanne Unverzagt, Ines Moldenhauer, Monika Nothacker, Dorothea Roßmeißl, Andreas V Hadjinicolaou, Frank Peinemann, Francesco Greco, Barbara Seliger
BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients...
May 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28504721/tumour-exosomes-from-cells-harbouring-ptprz1-met-fusion-contribute-to-a-malignant-phenotype-and-temozolomide-chemoresistance-in-glioblastoma
#18
A-L Zeng, W Yan, Y-W Liu, Z Wang, Q Hu, E Nie, X Zhou, R Li, X-F Wang, T Jiang, Y-P You
Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28504276/targeted-calcium-influx-boosts-cytotoxic-t-lymphocyte-function-in-the-tumour-microenvironment
#19
Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G de Rubio, Alan V Smrcka, Chang-Duk Jun, Woojin Jung, Byeonghak Park, Tae-Il Kim, Minsoo Kim
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca(2+) response...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28501561/the-sleeping-ugly-tumour-microenvironment-s-act-to-make-or-break-the-spell-of-dormancy
#20
REVIEW
Laurie Gay, Ilaria Malanchi
Metastasis is the main cause of death for most cancer patients. It appears clear from clinical observations that the majority of cancers, particularly carcinoma do not follow a linear model of metastatic progression, where cancer cells shed from the primary tumour, disseminate to a distant organ and immediately outgrow to form clinical metastasis. Certainly, while cancer spreading is an early event, metastasis occurs much later during tumour progression and frequently arises several years after primary tumour resection...
May 10, 2017: Biochimica et Biophysica Acta
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