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Tumor microenvironment

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https://www.readbyqxmd.com/read/28922358/quantifying-the-effects-of-antiangiogenic-and-chemotherapy-drug-combinations-on-drug-delivery-and-treatment-efficacy
#1
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/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
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/28921470/cgas-sting-activation-in-the-tumor-microenvironment-and-its-role-in-cancer-immunity
#3
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/28920957/klf4-dependent-perivascular-cell-plasticity-mediates-pre-metastatic-niche-formation-and-metastasis
#4
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/28920514/foe-or-friend-janus-faces-of-the-neurovascular-unit-in-the-formation-of-brain-metastases
#5
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/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28919985/human-tumor-derived-exosomes-tex-regulate-treg-functions-via-cell-surface-signaling-rather-than-uptake-mechanisms
#11
Laurent Muller, Patricia Simms, Chang-Sook Hong, Michael I Nishimura, Edwin K Jackson, Simon C Watkins, Theresa L Whiteside
Tumor-derived exosomes (TEX) are ubiquitously present in the tumor microenvironment and plasma of cancer patients. TEX carry a cargo of multiple stimulatory and inhibitory molecules and deliver them to recipient cells, serving as a communication network for the tumor. The mechanisms TEX use for delivering messages to recipient cells were evaluated using PKH26-labeled TEX produced by cultured human tumor cells, exosomes produced by dendritic cells-derived exosomes (DEX), or exosomes isolated from plasma of cancer patients (EXO)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919895/mind-the-gaps-in-tumor-immunity-impact-of-connexin-mediated-intercellular-connections
#12
REVIEW
María Alejandra Gleisner, Mariela Navarrete, Francisca Hofmann, Flavio Salazar-Onfray, Andrés Tittarelli
Gap junctions (GJs)-mediated intercellular communications (GJICs) are connexin (Cx)-formed plasma membrane channels that allow for the passage of small molecules between adjacent cells, and are involved in several physiopathological processes, including immune responses against cancer. In general, tumor cells are poorly coupled through GJs, mainly due to low Cx expression or reduced channel activity, suggesting that Cxs may have tumor suppressor roles. However, more recent data indicate that Cxs and/or GJICs may also in some cases promote tumor progression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919780/the-role-and-significance-of-vegfr2-regulatory-t-cells-in-tumor-immunity
#13
REVIEW
Panrong Zhu, Chenxi Hu, Kaiyuan Hui, Xiaodong Jiang
Tumor development is closely related to angiogenesis, and VEGFR2 plays an important role in tumor angiogenesis. It is broadly expressed in the blood vessels, especially in the microvessels of tumor tissues. Furthermore, VEGFR2 is detected on the surface of the cell membrane in various immune cells, such as dendritic cells, macrophages, and regulatory T cells (Tregs). Tregs, which are one of the key negative regulatory factors in tumor immune microenvironments, show high-level expression of VEGFR2 which participates in the regulation of immunosuppressive function...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919714/radium-223-dichloride-for-prostate-cancer-treatment
#14
REVIEW
Emmanuel Deshayes, Mathieu Roumiguie, Constance Thibault, Philippe Beuzeboc, Florent Cachin, Christophe Hennequin, Damien Huglo, François Rozet, Diana Kassab-Chahmi, Xavier Rebillard, Nadine Houédé
Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo(®)) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919575/an-integrative-model-of-prostate-cancer-interaction-with-the-bone-microenvironment
#15
A Farhat, D Jiang, D Cui, E T Keller, Trachette L Jackson
Despite advanced efforts in early diagnosis, aggressive surgical treatment, and use of targeted chemotherapies, the prognosis for many cancers is still dismal. This emphasizes the necessity to develop new strategies for understanding tumor growth and metastasis. Here we use a systems approach that combines mathematical modeling and numerical simulation to develop a predictive computational model for prostate cancer and its subversion of the bone microenvironment. This model simulates metastatic prostate cancer evolution, progressing from normal bone and hormone levels to quantifiable diseased states...
September 14, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28919508/pro-inflammatory-chitosan-poly-%C3%AE-glutamic-acid-nanoparticles-modulate-human-antigen-presenting-cells-phenotype-and-revert-their-pro-invasive-capacity
#16
Flávia Castro, Marta L Pinto, Andreia M Silva, Catarina L Pereira, Graciosa Q Teixeira, Maria Gomez-Lazaro, Susana G Santos, Mário A Barbosa, Raquel M Gonçalves, Maria J Oliveira
Anticancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals provided by antigen-presenting cells (APCs). However, it is described that immature dendritic cells (DCs) and macrophages at the tumor site may have an immunosuppressive profile, which limits the activity of effector T cells and supports tumor progression. Therapeutic targeting of these innate immune cells, either aiming at their elimination or re-polarization towards an immunostimulatory profile, has been pointed as an attractive approach to control tumor progression...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28918908/macrophage-biology-plays-a-central-role-during-ionizing-radiation-elicited-tumor-response
#17
REVIEW
Qiuji Wu, Awatef Allouch, Isabelle Martins, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied...
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28918906/radiotherapy-and-the-tumor-microenvironment-the-macro-picture
#18
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we explore the inner workings of tumor-associated macrophages and seek to understand how these cells can boost or limit the efficacy of radiotherapy, depending on the context. We also highlight a study revealing that staffing patterns in the intensive care unit may affect the outcome of patients with severe sepsis. Finally, we learn how an advanced imaging technique can improve endodontic treatment planning.
August 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28917532/effects-of-tumor-microenvironments-on-targeted-delivery-of-glycol-chitosan-nanoparticles
#19
Ji Young Yhee, Sangmin Jeon, Hong Yeol Yoon, Man Kyu Shim, Hyewon Ko, Jiwoong Min, Jin Hee Na, Hyeyoun Chang, Hyounkoo Han, Jong-Ho Kim, Minah Suh, Hyukjin Lee, Jae Hyung Park, Kwangmeyung Kim, Ick Chan Kwon
In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated...
September 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#20
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 12, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
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