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Tumour microenvironment

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https://www.readbyqxmd.com/read/28642603/imaging-of-anticancer-drug-action-in-single-cells
#1
REVIEW
Miles A Miller, Ralph Weissleder
Imaging is widely used in anticancer drug development, typically for whole-body tracking of labelled drugs to different organs or to assess drug efficacy through volumetric measurements. However, increasing attention has been drawn to pharmacology at the single-cell level. Diverse cell types, including cancer-associated immune cells, physicochemical features of the tumour microenvironment and heterogeneous cell behaviour all affect drug delivery, response and resistance. This Review summarizes developments in the imaging of in vivo anticancer drug action, with a focus on microscopy approaches at the single-cell level and translational lessons for the clinic...
June 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28642171/macrophage-migration-inhibitory-factor-promotes-osteosarcoma-growth-and-lung-metastasis-through-activating-the-ras-mapk-pathway
#2
Chen Wang, Xing Zhou, Wentao Li, Mingyue Li, Tingyue Tu, Ximing Ba, Yinyu Wu, Zhen Huang, Gentao Fan, Guangxin Zhou, Sujia Wu, Jianning Zhao, Junfeng Zhang, Jiangning Chen
Emerging evidence suggests that the tumour microenvironment plays a critical role in osteosarcoma (OS) development. Thus, cytokine immunotherapy could be a novel strategy for OS treatment. In this study, we explored the role of macrophage migration inhibitory factor (MIF), an important cytokine in OS progression, and investigated the anti-tumour effects of targeting MIF in OS. The results showed that MIF significantly increased in the tissue and serum samples of OS patients and was associated with tumour size, pulmonary metastasis and the survival rate of OS patients...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28639667/recent-progress-in-surface-enhanced-raman-spectroscopy-for-biological-and-biomedical-applications-from-cells-to-clinics
#3
REVIEW
D Cialla-May, X-S Zheng, K Weber, J Popp
The application of surface-enhanced Raman spectroscopy (SERS) in biological and biomedical detection schemes is feasible due to its excellent molecular specificity and high sensitivity as well as the capability of SERS to be performed in complex biological compositions. SERS-based investigation of cells, which are the basic structure and functional unit of organisms, represents the starting point of this review. It is demonstrated that SERS provides a deep understanding of living cells as well as their microenvironment which is needed to assess the development of diseases...
June 22, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28637915/tumour-on-a-chip-microfluidic-models-of-tumour-morphology-growth-and-microenvironment
#4
REVIEW
Hsieh-Fu Tsai, Alen Trubelja, Amy Q Shen, Gang Bao
Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28635961/hypoxia-induced-mobilization-of-nhe6-to-the-plasma-membrane-triggers-endosome-hyperacidification-and-chemoresistance
#5
Fabrice Lucien, Pierre-Paul Pelletier, Roxane R Lavoie, Jean-Michel Lacroix, Sébastien Roy, Jean-Luc Parent, Dominique Arsenault, Kelly Harper, Claire M Dubois
The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#6
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28629307/tumor-reversion-mesenchymal-epithelial-transition-as-a-critical-step-in-managing-the-tumor-microenvironment-cross-talk
#7
Mariano Bizzarri, Alessandra Cucina, Sara Proietti
Tumour reversion represents a promising field of investigation. The occurrence of cancer reversion both in vitro and in vivo has been ascertained by an increasing number of reports. The reverting process may be triggered in a wide range of different cancer types by both molecular and physical cues. This process encompasses mandatorily a change in the cell-stroma interactions, leading to profound modification in tissue architecture. Indeed, cancer reversion may be obtained by only resetting the overall burden of biophysical cues acting on the cell-stroma system, thus indicating that conformational changes induced by cell shape and cytoskeleton remodelling trigger downstream the cascade of molecular events required for phenotypic reversion...
June 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28629006/a-colon-targeted-drug-delivery-system-based-on-alginate-modificated-graphene-oxide-for-colorectal-liver-metastasis
#8
Bin Zhang, Yayuan Yan, Qiujuan Shen, Dong Ma, Langhuan Huang, Xiang Cai, Shaozao Tan
A major problem associated with colon cancer is liver metastasis. A colon-targeted drug delivery system is one way to address this problem after the resection of colorectal cancer. However, traditional drug delivery systems face many challenges, such as an inability to control the release rate, inaccurate targeting, susceptibility to the microenvironment and poor stability. Here, we report the development of a graphene oxide (GO)-based, sodium alginate (ALG) functionalized colon-targeting drug delivery system, that is loaded with 5-fluorouracil (5-FU) as the anti-cancer drug (denoted as GO-ALG/5-FU)...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28621843/metabolic-reprogramming-in-the-tumour-microenvironment-a-hallmark-shared-by-cancer-cells-and-t-lymphocytes
#9
REVIEW
Katrina E Allison, Brenda L Coomber, Byram W Bridle
Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and upregulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system...
June 16, 2017: Immunology
https://www.readbyqxmd.com/read/28615369/clinical-development-of-pd-1-pd-l1-immunotherapy-for-gastrointestinal-cancers-facts-and-hopes
#10
Ian Chau
Gastrointestinal (GI) cancers are among the most deadly malignancies. Whereas serial incremental survival benefits have been made with cytotoxic chemotherapy with metastatic disease, a plateau of achievement has been reached. Applying modern integrative genomic technology, distinct molecular subgroups have been identified in GI cancers. This not only highlighted the heterogeneity in tumours of each primary anatomical site, it also identified novel therapeutic targets in distinct molecular subgroups and might improve the yield of clinical success...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611201/relationship-of-the-breast-ductal-carcinoma-in-situ-immune-microenvironment-with-clinico-pathological-and-genetic-features
#11
Shona Hendry, Jia-Min B Pang, David Byrne, Sunil R Lakhani, Margaret C Cummings, Ian G Campbell, G Bruce Mann, Kylie L Gorringe, Stephen B Fox
The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown. <br /><br />Experimental Design: We quantified tumour associated lymphocytes (TILs) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases respectively), some of which had copy number (n=55) and mutation data (n=20). <br /><br />Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range 0-90%)...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599269/inhibition-of-extracellular-matrix-mediated-tgf-%C3%AE-signalling-suppresses-endometrial-cancer-metastasis
#12
Subhransu S Sahoo, Min Yuan Quah, Sarah Nielsen, Joshua Atkins, Gough G Au, Murray J Cairns, Pravin Nahar, Janine M Lombard, Pradeep S Tanwar
Although aggressive invasion and distant metastases are an important cause of morbidity and mortality in patients with endometrial cancer (EC), the requisite events determining this propensity are currently unknown. Using organotypic three-dimensional culture of endometrial cancer cell lines, we demonstrated anti-correlated TGF-β signalling gene expression patterns that arise among extracellular matrix (ECM)-attached cells. TGF-β pathway seemed to be active in EC cells forming non-glandular colonies in 3D-matrix but weaker in glandular colonies...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597546/endothelin-1-receptor-blockade-as-new-possible-therapeutic-approach-in-multiple-myeloma
#13
Anna Russignan, Cecilia Spina, Nicola Tamassia, Adriana Cassaro, Antonella Rigo, Anna Bagnato, Laura Rosanò, Angela Bonalumi, Michele Gottardi, Lucia Zanatta, Alice Giacomazzi, Maria Teresa Scupoli, Martina Tinelli, Ugo Salvadori, Federico Mosna, Alberto Zamò, Marco A Cassatella, Fabrizio Vinante, Cristina Tecchio
New effective treatments are needed to improve outcomes for multiple myeloma (MM) patients. Receptors with restricted expression on plasma cells (PCs) represent attractive new therapeutic targets. The endothelin-1 (EDN1) axis, consisting of EDN1 acting through EDN-receptor A (EDNRA) and B (EDNRB), was previously shown to be overexpressed in several tumours, including MM. However, there is incomplete understanding of how EDN1 axis regulates MM growth and response to therapy. Besides EDNRA, the majority of MM cell lines and primary malignant PCs express high levels of EDNRB and release EDN1...
June 9, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28593737/influence-of-opioids-on-immune-function-in-patients-with-cancer-pain-from-bench-to-bedside
#14
REVIEW
Jason W Boland, A Graham Pockley
In patients with cancer, opioids are principally used for the management of acute surgical and chronic cancer-related pain. However, opioids have many non-analgesic effects, including direct and indirect effects on cancer cells and on anti-tumour immunity (natural killer (NK) cells, macrophages and T-cells). Direct effects on immune cells are manifested via opioid and non-opioid Toll-like receptors, whereas indirect effects are manifested via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis...
June 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28592821/development-of-a-3d-angiogenesis-model-to-study-tumour-endothelial-cell-interactions-and-the-effects-of-anti-angiogenic-drugs
#15
Arno Amann, Marit Zwierzina, Stefan Koeck, Gabriele Gamerith, Elisabeth Pechriggl, Julia M Huber, Edith Lorenz, Jens M Kelm, Wolfgang Hilbe, Heinz Zwierzina, Johann Kern
The tumour microenvironment and tumour angiogenesis play a critical role in the development and therapy of many cancers, but in vitro models reflecting these circumstances are rare. In this study, we describe the development of a novel tri-culture model, using non-small cell lung cancer (NSCLC) cell lines (A549 and Colo699) in combination with a fibroblast cell line (SV 80) and two different endothelial cell lines in a hanging drop technology. Endothelial cells aggregated either in small colonies in Colo699 containing microtissues or in tube like structures mainly in the stromal compartment of microtissues containing A549...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28589318/matricellular-proteins-in-cancer-a-focus-on-secreted-frizzled-related-proteins
#16
Krista Marie Vincent, Lynne-Marie Postovit
Tumours are complex entities, wherein cancer cells interact with myriad soluble, insoluble and cell associated factors. These microenvironmental mediators regulate tumour growth, progression and metastasis, and are produced by cancer cells and by stromal components such as fibroblast, adipocytes and immune cells. Through their ability to bind to extracellular matrix proteins, cell surface receptors and growth factors, matricellular proteins enable a dynamic reciprocity between cancer cells and their microenvironment...
June 7, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28585775/the-roles-of-the-pd-1-pd-l1-pathway-at-immunologically-privileged-sites
#17
Li-Ling Wang, Zhi-Hui Li, Xiao-Hui Hu, Kahinho P Muyayalo, Yong-Hong Zhang, Ai-Hua Liao
The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response...
June 6, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28585612/-recent-advances-of-immunooncology-in-the-treatment-of-solid-tumours-and-haematological-malignancies-the-immune-checkpoint-inhibitors
#18
Viktória Fésüs
Cancer immunotherapy is coming of age, as outstanding results can be achieved in the therapy of cancer with poor prognosis by altering the patients' immune system and by promoting the immune response against tumours. Amongst immunotherapies, the immune checkpoint inhibitors (ICI) proved to be the most effective, primarily in the treatment of solid tumours, including melanoma, non-small cell lung carcinoma, and classical Hodgkin's lymphoma. The reason for this efficacy is the immunosuppressive microenvironment typical for many cancer types, directly and indirectly inhibiting effector T-cell responses...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28585308/immunosurveillance-profile-of-oral-squamous-cell-carcinoma-and-oral-epithelial-dysplasia-through-dendritic-and-t-cells-analysis
#19
Ana Carolina Amorim Pellicioli, Lynne Bingle, Paula Farthing, Márcio Ajudarte Lopes, Manoela Domingues Martins, Pablo Agustin Vargas
Oral squamous cell carcinomas (OSCC) can arise from potentially malignant disorders, such as leukoplakia. The immune system plays an important role recognizing tumour precursor cells. However, due to immunoediting mechanisms cancer cells are able to escape immune system surveillance. OBJECTIVE: Evaluate the profile of dendritic (Langerhans and plasmacytoid) and T cells in OSCC and oral epithelial dysplasia (OED) and correlate these findings with clinical data. MATERIALS AND METHODS: Fifty cases of OSCC and 48 of OED were immunostained for CD1a and CD83 dendritic Langerhans cells (DLC), plasmacytoid dendritic cells (pDC) CD303 and CD8 followed by quantitative analysis...
June 5, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28583218/demodex-canis-regulates-cholinergic-system-mediated-immunosuppressive-pathways-in-canine-demodicosis
#20
P Kumari, R Nigam, A Singh, U P Nakade, A Sharma, S K Garg, S K Singh
Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study...
June 6, 2017: Parasitology
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