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https://www.readbyqxmd.com/read/28922717/magnetic-nanoparticle-loaded-alginate-beads-for-local-micro-actuation-of-in-vitro-tissue-constructs
#1
Awatef M Alshehri, Otto C Wilson, Bishnu Dahal, John Philip, Xiaolong Luo, Christopher B Raub
Magnetic nanoparticles (MNPs) self-align and transduce magnetic force, two properties which lead to promising applications in cell and tissue engineering. However, the toxicity of MNPs to cells which uptake them is a major impediment to applications in engineered tissue constructs. To address this problem, MNPs were embedded in millimeter-scale alginate beads, coated with glutaraldehyde cross-linked chitosan, and loaded in acellular and MDA-MB-231 cancer cell-seeded collagen hydrogels, providing local micro-actuation under an external magnetic field...
September 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28922523/mature-b-cells-accelerate-wound-healing-after-acute-and-chronic-diabetic-skin-lesions
#2
Ruxandra F Sîrbulescu, Chloe K Boehm, Erin Soon, Moses Q Wilks, Iulian Ilieş, Hushan Yuan, Ben Maxner, Nicolas Chronos, Charalambos Kaittanis, Marc D Normandin, Georges El Fakhri, Dennis P Orgill, Ann E Sluder, Mark C Poznansky
Chronic wounds affect 12-15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here we demonstrate that purified mature naïve B220(+) /CD19(+) /IgM(+) /IgD(+) B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2-3 days in wild-type mice and 5-6 days in obese diabetic mice. The treatment led to full closure in 43% of chronic diabetic wounds, as compared to only 5% in saline-treated controls...
September 18, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28922497/mutual-independence-of-alkaline-and-calcium-mediated-signalling-in-aspergillus-fumigatus-refutes-the-existence-of-a-conserved-druggable-signalling-nexus
#3
Omar Loss, Margherita Bertuzzi, Yu Yan, Natalie Fedorova, Bethany L McCann, Darius Armstrong-James, Eduardo A Espeso, Nick D Read, William C Nierman, Elaine M Bignell
Functional coupling of calcium- and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca(2+) , such that highly conserved regulators of both calcium- (Crz) and pH- (PacC/Rim) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti-infectives, abrogation of alkaline signalling has therefore been postulated as an adjunctive antifungal strategy...
September 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28922408/the-role-of-the-pi3k-akt-signaling-pathway-in-the-developmental-competence-of-bovine-oocytes
#4
Gabriella Mamede Andrade, Juliano Coelho da Silveira, Claudia Perrini, Maite Del Collado, Samuel Gebremedhn, Dawit Tesfaye, Flávio Vieira Meirelles, Felipe Perecin
The ovarian follicle encloses oocytes in a microenvironment throughout their growth and acquisition of competence. Evidence suggests a dynamic interplay among follicular cells and oocytes, since they are constantly exchanging "messages". We dissected bovine ovarian follicles and recovered follicular cells (FCs-granulosa and cumulus cells) and cumulus-oocyte complexes (COCs) to investigate whether the PI3K-Akt signaling pathway impacted oocyte quality. Following follicle rupture, COCs were individually selected for in vitro cultures to track the follicular cells based on oocyte competence to reach the blastocyst stage after parthenogenetic activation...
2017: PloS One
https://www.readbyqxmd.com/read/28922358/quantifying-the-effects-of-antiangiogenic-and-chemotherapy-drug-combinations-on-drug-delivery-and-treatment-efficacy
#5
Sirin Yonucu, Defne Yιlmaz, Colin Phipps, Mehmet Burcin Unlu, Mohammad Kohandel
Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise...
September 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28922170/a-critical-assessment-of-exosomes-in-the-pathogenesis-and-stratification-of-parkinson-s-disease
#6
George K Tofaris
Extracellular vesicles including exosomes are released by a variety of cell types including neurons and exhibit molecular profiles that reflect normal and disease states. As their content represents a snapshot of the intracellular milieu, they could be exploited as biomarkers of the otherwise inaccessible brain microenvironment. In addition they may contribute to the progression of neurodegenerative disorders by facilitating the spread of misfolded proteins at distant sites or activating immune cells. This review summarizes recent advances in the study of exosomes in Parkinson's disease pathophysiology and their potential as disease biomarkers...
September 11, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#7
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#8
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28921470/cgas-sting-activation-in-the-tumor-microenvironment-and-its-role-in-cancer-immunity
#9
Geneviève Pépin, Michael P Gantier
Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Nonetheless, STING appears to be an essential component in the recruitment of immune cells to the tumor microenvironment, which is paramount to immune clearance of the tumor...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28921309/lung-cancer-associated-brain-metastasis-molecular-mechanisms-and-therapeutic-options
#10
REVIEW
Meysam Yousefi, Tayyeb Bahrami, Arash Salmaninejad, Rahim Nosrati, Parisa Ghaffari, Seyed H Ghaffari
BACKGROUND: Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease...
September 18, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28920957/klf4-dependent-perivascular-cell-plasticity-mediates-pre-metastatic-niche-formation-and-metastasis
#11
Meera Murgai, Wei Ju, Matthew Eason, Jessica Kline, Daniel W Beury, Sabina Kaczanowska, Markku M Miettinen, Michael Kruhlak, Haiyan Lei, Jack F Shern, Olga A Cherepanova, Gary K Owens, Rosandra N Kaplan
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920955/mir-25-93-mediates-hypoxia-induced-immunosuppression-by-repressing-cgas
#12
Min-Zu Wu, Wei-Chung Cheng, Su-Feng Chen, Shin Nieh, Carolyn O'Connor, Chia-Lin Liu, Wen-Wei Tsai, Cheng-Jang Wu, Lorena Martin, Yaoh-Shiang Lin, Kou-Juey Wu, Li-Fan Lu, Juan Carlos Izpisua Belmonte
The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA...
September 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28920587/complement-in-cancer-untangling-an-intricate-relationship
#13
REVIEW
Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, Alberto Mantovani, John D Lambris
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28920514/foe-or-friend-janus-faces-of-the-neurovascular-unit-in-the-formation-of-brain-metastases
#14
Imola Wilhelm, Csilla Fazakas, Kinga Molnár, Attila G Végh, János Haskó, István A Krizbai
Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28920437/real-time-metabolic-interactions-between-two-bacterial-species-using-a-carbon-based-ph-microsensor-as-a-scanning-electrochemical-microscopy-secm-probe
#15
Vrushali Subhash Joshi, Partha Sarathi Sheet, Nyssa Cullin, Jens Kreth, Dipankar Koley
We have developed a carbon-based, fast-response potentiometric pH microsensor for use as a scanning electrochemical microscopy (SECM) chemical probe to quantitatively map the microbial metabolic exchange between two bacterial species, commensal Streptococcus gordonii and pathogenic Streptococcus mutans. The 25-μm diameter H+ ion-selective microelectrode or pH microprobe showed a Nernstian slope of 59 mV/pH and high selectivity against major ions such Na+, K+, Ca2+ and Mg2+. In addition, the unique conductive membrane composition aided us in performing an amperometric approach curve to position the probe and obtain a high-resolution pH map of the microenvironment produced by the lactate-producing S...
September 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#16
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920001/zoledronic-acid-inhibits-nfat-and-il-2-signaling-pathways-in-regulatory-t-cells-and-diminishes-their-suppressive-function-in-patients-with-metastatic-cancer
#17
Dhifaf Sarhan, Caroline Leijonhufvud, Shannon Murray, Kristina Witt, Christina Seitz, Majken Wallerius, Hanjing Xie, Anders Ullén, Ulrika Harmenberg, Elisabet Lidbrink, Charlotte Rolny, John Andersson, Andreas Lundqvist
Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919998/reciprocal-influence-of-b-cells-and-tumor-macro-and-microenvironments-in-the-apc-min-model-of-colorectal-cancer
#18
Francesca Mion, Stefania Vetrano, Silvia Tonon, Viviana Valeri, Andrea Piontini, Alessia Burocchi, Luciana Petti, Barbara Frossi, Alessandro Gulino, Claudio Tripodo, Mario P Colombo, Carlo E Pucillo
One of the most fascinating aspects of the immune system is its dynamism, meant as the ability to change and readapt according to the organism needs. Following an insult, we assist to the spontaneous organization of different immune cells which cooperate, locally and at distance, to build up an appropriate response. Throughout tumor progression, adaptations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion and metastasis to distal organs, but also to dramatic changes in the activity and composition of the immune system...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919997/increased-infiltration-and-tolerised-antigen-specific-cd8-tem-cells-in-tumor-but-not-peripheral-blood-have-no-impact-on-survival-of-hcmv-glioblastoma-patients
#19
M Bahador, A Gras Navarro, M A Rahman, M Dominguez-Valentin, S Sarowar, E Ulvestad, G Njølstad, S A Lie, E K Kristoffersen, E Bratland, M Chekenya
Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919987/programmed-death-ligand-1-pd-l1-expression-influences-the-immune-tolerogenic-microenvironment-in-antiretroviral-therapy-refractory-kaposi-s-sarcoma-a-pilot-study
#20
Salvinia Mletzko, David J Pinato, Rebecca C Robey, Alessia Dalla Pria, Peter Benson, Nesrina Imami, Mark Bower
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape...
2017: Oncoimmunology
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