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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323572/bilateral-changes-in-deep-tissue-environment-after-manual-lymphatic-drainage-in-patients-with-breast-cancer-treatment-related-lymphedema
#2
Paula M C Donahue, Rachelle Crescenzi, Allison O Scott, Vaughn Braxton, Aditi Desai, Seth A Smith, John Jordi, Ingrid M Meszoely, Ana M Grau, Rondi M Kauffmann, Raeshell S Sweeting, Kandace Spotanski, Sheila H Ridner, Manus J Donahue
BACKGROUND: Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD)...
March 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28323500/strategies-to-target-glucose-metabolism-in-tumor-microenvironment-on-cancer-by-flavonoids
#3
Gang Wang, Jun-Jie Wang, Rui Guan, Li Du, Jing Gao, Xing-Li Fu
The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted. Thus, the identification of flavonoids targeting alternative glucose metabolism pathways in TME may represent an attractive approach to the more effective therapeutic strategies for cancer...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28323411/engineering-an-injectable-muscle-specific-microenvironment-for-improved-cell-delivery-using-a-nanofibrous-extracellular-matrix-hydrogel
#4
Nikhil Rao, Gillie Agmon, Matthew T Tierney, Jessica L Ungerleider, Rebecca L Braden, Alessandra Sacco, Karen L Christman
Injection of skeletal muscle progenitors has the potential to be a minimally invasive treatment for a number of diseases that negatively affect vasculature and skeletal muscle, including peripheral artery disease (PAD). However, success with this approach has been limited because of poor transplant cell survival. This is primarily attributed to cell death due to extensional flow through the needle, the harsh ischemic environment of the host tissue, a deleterious immune cell response, and a lack of biophysical cues supporting exogenous cell viability...
March 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28319647/cancer-specific-intracellular-reductive-activation-of-anticancer-pt-iv-prodrugs
#5
Andriy Mokhir, Viktor Reshetnikov, Steffen Daum
Since cellular uptake of anticancer Pt(II)- and Pt(IV)-drugs occurs via different mechanisms, the latter ones can exhibit substantial activity towards cells, which have either intrinsic or acquired resistance towards Pt(II)-drugs. However, this positive effect is diminished due to reductive activation of Pt(IV)-drugs in extracellular space that can be one of the reasons why they were not yet approved for clinical use despite over 60 clinical trials conducted worldwide. Herein we suggest a solution to this problem by achieving highly specific intracellular versus extracellular prodrug reduction...
March 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28319464/the-dr-jekyll-and-mr-hyde-complexity-of-the-macrophage-response-in-disease
#6
Danielle Y F Twum, Lauren Burkard-Mandel, Scott I Abrams
Macrophages comprise a highly diverse cell population expressing a continuum of biologic activities dictated by exposure to a plethora of inflammatory cues. Moreover, in contrast to most other hematopoietic populations, macrophages can arise from multiple sites-namely, the bone marrow or yolk sac, adding to the complexity of macrophage biology during health and disease. Nonetheless, it is this very type of diversity that is indispensable for macrophages to respond effectively to pathologic insults. Most of the interest in macrophage biology has been devoted to bone marrow-derived populations, but it is now becoming clearer that tissue-resident populations, which arise from distinct hematopoietic compartments, serve critical roles in host defense, including protection against neoplastic disease...
February 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28319183/an-integrated-analysis-of-micro-and-macro-habitat-features-as-a-tool-to-detect-weather-driven-constraints-a-case-study-with-cavity-nesters
#7
D Campobello, J Lindström, R Di Maggio, M Sarà
The effects of climate change on animal populations may be shaped by habitat characteristics at both micro- and macro-habitat level, however, empirical studies integrating these two scales of observation are lacking. As analyses of the effects of climate change commonly rely on data from a much larger scale than the microhabitat level organisms are affected at, this mismatch risks hampering progress in developing understanding of the details of the ecological and evolutionary responses of organisms and, ultimately, effective actions to preserve their populations...
2017: PloS One
https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#8
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28318896/role-of-ahr-and-hif-1%C3%AE-in-glioblastoma-metabolism
#9
REVIEW
Galina Gabriely, Michael A Wheeler, Maisa C Takenaka, Francisco J Quintana
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling...
March 16, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#10
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#11
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#12
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28318131/hydrologic-refugia-plants-and-climate-change
#13
REVIEW
Blair C McLaughlin, David D Ackerly, P Zion Klos, Jennifer Natali, Todd E Dawson, Sally E Thompson
Climate, physical landscapes, and biota interact to generate heterogeneous hydrologic conditions in space and over time, which are reflected in spatial patterns of species distributions. As these species distributions respond to rapid climate change, microrefugia may support local species persistence in the face of deteriorating climatic suitability. Recent focus on temperature as a determinant of microrefugia insufficiently accounts for the importance of hydrologic processes and changing water availability with changing climate...
March 20, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28318017/thymic-crosstalk-restrains-the-pool-of-cortical-thymic-epithelial-cells-with-progenitor-properties
#14
Catarina Meireles, Ana R Ribeiro, Rute D Pinto, Catarina Leitão, Pedro M Rodrigues, Nuno L Alves
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs)...
March 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28317948/local-remodeling-of-synthetic-extracellular-matrix-microenvironments-by-co-cultured-endometrial-epithelial-and-stromal-cells-enables-long-term-dynamic-physiological-function
#15
Christi D Cook, Abby S Hill, Margaret Guo, Linda Stockdale, Julia P Papps, Keith B Isaacson, Douglas A Lauffenburger, Linda G Griffith
Mucosal barrier tissues, comprising a layer of tightly-bonded epithelial cells in intimate molecular communication with an underlying matrix-rich stroma containing fibroblasts and immune cells, are prominent targets for drugs against infection, chronic inflammation, and other disease processes. Although human in vitro models of such barriers are needed for mechanistic studies and drug development, differences in extracellular matrix (ECM) needs of epithelial and stromal cells hinder efforts to create such models...
March 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28317401/biological-implications-and-clinical-value-of-mir-210-in-gastrointestinal-cancer
#16
Wanli Yang, Jiaojiao Ma, Wei Zhou, Xin Zhou, Bo Cao, Daiming Fan, Liu Hong
Introduction Hypoxia, a common feature of tumor microenvironment, is known to accelerate tumor development and growth by promoting the formation of a neoplastic environment. Recent studies have provided a wealth of evidence that miRNAs are significant members of the adaptive response to low oxygen in tumors. miR-210 is one of the hypoxia-induced miRNAs, which has been reported extensively in cancer researches. However, there is no systematic discussion about the role of miR-210 in gastrointestinal cancer. We conducted a literature research in database including PubMed, Elsevier Science Direct and Medline before September 16, 2016, in order to collect articles of miR-210 in gastrointestinal cancer...
March 18, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28317367/-role-of-small-noncoding-rna-in-the-regulation-of-bacterial-virulence
#17
Wang Lu, Zheng Xin, Wang Shida, Li Jiyao, Xu Xin
In the long-term interaction between pathogens and host, the pathogens regulate the expression of related viru-lence genes to fit the host environment in response to the changes in the host microenvironment. Gene expression was believed to be controlled mainly at the level of transcription initiation by repressors or activators. Recent studies have revealed that small noncoding RNAs (sRNAs) are key regulators in bacterial pathogenesis. sRNA in bacteria is a noncoding RNA with length ranging from 50 to 500 nucleotides...
August 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28317261/diffusion-relaxation-correlation-spectroscopic-imaging-a-multidimensional-approach-for-probing-microstructure
#18
Daeun Kim, Eamon K Doyle, Jessica L Wisnowski, Joong Hee Kim, Justin P Haldar
PURPOSE: To propose and evaluate a novel multidimensional approach for imaging subvoxel tissue compartments called Diffusion-Relaxation Correlation Spectroscopic Imaging. THEORY AND METHODS: Multiexponential modeling of MR diffusion or relaxation data is commonly used to infer the many different microscopic tissue compartments that contribute signal to macroscopic MR imaging voxels. However, multiexponential estimation is known to be difficult and ill-posed. Observing that this ill-posedness is theoretically reduced in higher dimensions, diffusion-relaxation correlation spectroscopic imaging uses a novel multidimensional imaging experiment that jointly encodes diffusion and relaxation information, and then uses a novel constrained reconstruction technique to generate a multidimensional diffusion-relaxation correlation spectrum for every voxel...
March 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28317128/comparison-of-dce-mri-kinetic-parameters-and-fmiso-pet-uptake-parameters-in-head-and-neck-cancer-patients
#19
Urban Simoncic, Sara Leibfarth, Stefan Welz, Nina Schwenzer, Holger Schmidt, Gerald Reischl, Christina Pfannenberg, Christian la Fougère, Konstantin Nikolaou, Daniel Zips, Daniela Thorwarth
PURPOSE: Tumour hypoxia is a major cause of radiation resistance, often present in various solid tumours. Dynamic [(18) F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumour hypoxia. Comprehensive characterization of tumour microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters...
March 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#20
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
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