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Tumor dormancy

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https://www.readbyqxmd.com/read/28868144/inhibition-of-il-17a-by-secukinumab-shows-no-evidence-of-increased-mycobacterium-tuberculosis-infections
#1
Michael Kammüller, Tsen-Fang Tsai, Christopher Em Griffiths, Nidhi Kapoor, Pappachan E Kolattukudy, Dominique Brees, Salah-Dine Chibout, Jorge Safi, Todd Fox
Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis...
August 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28839232/urokinase-type-plasminogen-activator-receptor-upar-expression-enhances-invasion-and-metastasis-in-ras-mutated-tumors
#2
Concetta Di Mauro, Ada Pesapane, Luigi Formisano, Roberta Rosa, Valentina D'Amato, Paola Ciciola, Alberto Servetto, Roberta Marciano, Roberta Clara Orsini, Francesca Monteleone, Nicola Zambrano, Gabriella Fontanini, Adele Servadio, Giuseppe Pignataro, Lucia Grumetto, Antonio Lavecchia, Dario Bruzzese, Antonino Iaccarino, Giancarlo Troncone, Bianca Maria Veneziani, Nunzia Montuori, Sabino De Placido, Roberto Bianco
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814453/sympathetic-signaling-reactivates-quiescent%C3%A2-disseminated-prostate-cancer-cells-in-the-bone-marrow
#3
Ann Decker, Younghun Jung, Frank C Cackowski, Kenji Yumoto, Jingcheng Wang, Russell S Taichman
Clinical observations have identified an association between psychological stress and cancer relapse; suggesting that the sympathetic nervous system/norepinephrine (NE) plays a role in reactivation of dormant disseminated tumor cells (DTCs) in the bone marrow niche. Here, the mechanism by which NE regulates prostate cancer (PCa) DTCs in the marrow is explored. NE directly stimulated PCa cell proliferation through β2-adrenergic receptors (ADRB2). NE also altered PCa proliferation in the marrow niche by indirectly by downregulating the secretion of the dormancy inducing molecule growth arrest specific-6 (GAS6) expressed by osteoblasts...
August 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28779846/immune-modulation-by-a-cellular-network-of-mesenchymal-stem-cells-and-breast-cancer-cell-subsets-implication-for-cancer-therapy
#4
Hussam S Eltoukhy, Garima Sinha, Caitlyn A Moore, Oleta A Sandiford, Pranela Rameshwar
The immune modulatory properties of mesenchymal stem cells (MSCs) are mostly controlled by the particular microenvironment. Cancer stem cells (CSCs), which can initiate a clinical tumor, have been the subject of intense research. This review article discusses investigative studies of the roles of MSCs on cancer biology including on CSCs, and the potential as drug delivery to tumors. An understanding of how MSCs behave in the tumor microenvironment to facilitate the survival of tumor cells would be crucial to identify drug targets...
August 1, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28775230/characterization-and-functional-analysis-of-a-slow-cycling-subpopulation-in-colorectal-cancer-enriched-by-cell-cycle-inducer-combined-chemotherapy
#5
Feng-Hua Wu, Lei Mu, Xiao-Lan Li, Yi-Bing Hu, Hui Liu, Lin-Tao Han, Jian-Ping Gong
The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766939/hypoxia-responsive-cobalt-complexes-in-tumor-spheroids-laser-ablation-inductively-coupled-plasma-mass-spectrometry-and-magnetic-resonance-imaging-studies
#6
Edward S O'Neill, Amandeep Kaur, David P Bishop, Dmitry Shishmarev, Philip W Kuchel, Stuart M Grieve, Gemma A Figtree, Anna K Renfrew, Paul D Bonnitcha, Elizabeth J New
Dense tumors are resistant to conventional chemotherapies due to the unique tumor microenvironment characterized by hypoxic regions that promote cellular dormancy. Bioreductive drugs that are activated in response to this hypoxic environment are an attractive strategy for therapy with anticipated lower harmful side effects in normoxic healthy tissue. Cobalt bioreductive pro-drugs that selectively release toxic payloads upon reduction in hypoxic cells have shown great promise as anticancer agents. However, the bioreductive response in the tumor microenvironment must be better understood, as current techniques for monitoring bioreduction to Co(II) such as X-ray absorption near-edge structure and extended X-ray absorption fine structure provide limited information on speciation and require synchrotron radiation sources...
August 2, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28756304/chemomechanically-engineered-3d-organotypic-platforms-of-bladder-cancer-dormancy-and-reactivation
#7
Taraka Sai Pavan Grandhi, Thrimoorthy Potta, Rajeshwar Nitiyanandan, Indrani Deshpande, Kaushal Rege
Tumors undergo periods of dormancy followed by reactivation leading to metastatic disease. Arrest in the G0/G1 phase of the cell cycle and resistance to chemotherapeutic drugs are key hallmarks of dormant tumor cells. Here, we describe a 3D platform of bladder cancer cell dormancy and reactivation facilitated by a novel aminoglycoside-derived hydrogel, Amikagel. These 3D dormant tumor microenvironments (3D-DTMs) were arrested in the G0/G1 phase and were highly resistant to anti-proliferative drugs. Inhibition of targets in the cellular protein production machinery led to induction of endoplasmic reticulum (ER) stress and complete ablation of 3D-DTMs...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28741495/adaptive-stress-responses-during-tumor-metastasis-and-dormancy
#8
REVIEW
Daniela Senft, Ze'ev A Ronai
To survive inhospitable environments, tumor cells are forced to remodel their signaling pathways by altering transcription, translation, and post-translational modifications. This adaptation is regulated in a spatial and temporal manner and gives rise to individual tumor cells with distinct gene expression and metabolic signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity, which-together with the genetic background of the tumor-determines whether cells resist environmental stress, enter dormancy, or metastasize...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#9
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28715713/metastasis-systems-biology-how-are-macro-environmental-signals-transmitted-into-microenvironmental-cues-for-disseminated-tumor-cells
#10
REVIEW
Candice Alexandra Grzelak, Cyrus Michael Ghajar
Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one...
October 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28693495/an-agent-based-model-of-triple-negative-breast-cancer-the-interplay-between-chemokine-receptor-ccr5-expression-cancer-stem-cells-and-hypoxia
#11
Kerri-Ann Norton, Travis Wallace, Niranjan B Pandey, Aleksander S Popel
BACKGROUND: Triple-negative breast cancer lacks estrogen, progesterone, and HER2 receptors and is thus not possible to treat with targeted therapies for these receptors. Therefore, a greater understanding of triple-negative breast cancer is necessary for the treatment of this cancer type. In previous work from our laboratory, we found that chemokine ligand-receptor CCL5-CCR5 axis is important for the metastasis of human triple-negative breast cancer cell MDA-MB-231 to the lymph nodes and lungs, in a mouse xenograft model...
July 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28678198/virus-host-cell-crosstalk-in-hypoxic-hpv-positive-cancer-cells
#12
REVIEW
Karin Hoppe-Seyler, Julia Mändl, Svenja Adrian, Bianca J Kuhn, Felix Hoppe-Seyler
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The expression of the viral E6/E7 oncogenes plays a key role for HPV-linked oncogenesis. It recently has been found that low oxygen concentrations ("hypoxia"), as present in sub-regions of HPV-positive cancers, strongly affect the interplay between the HPV oncogenes and their transformed host cell. As a result, a state of dormancy is induced in hypoxic HPV-positive cancer cells, which is characterized by a shutdown of viral oncogene expression and a proliferative arrest that can be reversed by reoxygenation...
July 5, 2017: Viruses
https://www.readbyqxmd.com/read/28636984/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#13
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m2, d1 plus oral cyclophosphamide 50 mg daily) or T alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28599500/notable-roles-of-ezh2-and-dnmt1-in-epigenetic-dormancy-of-the-shp1-gene-during-the-progression-of-chronic-myeloid-leukaemia
#14
Jing Wang, Luoming Hua, Ming Guo, Lin Yang, Xiaojun Liu, Yanmeng Li, Xiaoyan Shang, Jianmin Luo
Tumor development is associated with the methylation of cytosine-guanine (CpG) islands. The occurrence of methylation requires several factors, such as DNA methylation systems and polycomb group (PcG) proteins. At present, novel drugs are needed for the treatment of chronic myeloid leukaemia (CML), particularly considering the current prognosis of CML. The methylation status of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1) gene, a negative regulator of signal transduction, has been identified as being altered in numerous haematological malignancies...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28585066/modeling-the-dichotomy-of-the-immune-response-to-cancer-cytotoxic-effects-and-tumor-promoting-inflammation
#15
Kathleen P Wilkie, Philip Hahnfeldt
Although the immune response is often regarded as acting to suppress tumor growth, it is now clear that it can be both stimulatory and inhibitory. The interplay between these competing influences has complex implications for tumor development, cancer dormancy, and immunotherapies. In fact, early immunotherapy failures were partly due to a lack in understanding of the nonlinear growth dynamics these competing immune actions may cause. To study this biological phenomenon theoretically, we construct a minimally parameterized framework that incorporates all aspects of the immune response...
June 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28516343/therapeutic-dormancy-to-delay-postsurgical-glioma-recurrence-the-past-present-and-promise-of-focal-hypothermia
#16
REVIEW
Didier Wion
Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for glioma. However, despite multimodal treatment, most glioma patients die from local recurrence in the resection margin. Glioma surgery is inherently lesional, and the response of brain tissue to surgery includes hemostasis, angiogenesis, reactive gliosis and inflammation. Unfortunately, these processes are also associated with tumorigenic side-effects. An increasing amount of evidence indicates that the response to a surgery-related brain injury is hijacked by residual glioma cells and participates in the local regeneration of tumor tissues at the resection margin...
July 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28507050/tumor-dormancy-and-relapse-from-a-natural-byproduct-of-evolution-to-a-disease-state
#17
REVIEW
Masoud H Manjili
Species evolve by mutations and epigenetic changes acting on individuals in a population; tumors evolve by similar mechanisms at a cellular level in a tissue. This article reviews growing evidence about tumor dormancy and suggests that (i) cellular malignancy is a natural byproduct of evolutionary mechanisms, such as gene mutations and epigenetic modifications, which is manifested in the form of tumor dormancy in healthy individuals as well as in cancer survivors; (ii) cancer metastasis could be an early dissemination event that could occur during malignant dormancy even before primary cancer is clinically detectable; and (iii) chronic inflammation is a key factor in awakening dormant malignant cells at the primary site, leading to primary cancer development, and at distant sites, leading to advanced stage diseases...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28488695/blockade-of-ido-kynurenine-ahr-metabolic-circuitry-abrogates-ifn-%C3%AE-induced-immunologic-dormancy-of-tumor-repopulating-cells
#18
Yuying Liu, Xiaoyu Liang, Xiaonan Yin, Jiadi Lv, Ke Tang, Jingwei Ma, Tiantian Ji, Huafeng Zhang, Wenqian Dong, Xun Jin, Degao Chen, Yanchun Li, Songyan Zhang, Heidi Q Xie, Bin Zhao, Tong Zhao, Jinzhi Lu, Zhuo-Wei Hu, Xuetao Cao, F Xiao-Feng Qin, Bo Huang
Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#19
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410147/the-roles-of-microglia-macrophages-in-tumor-progression-of-brain-cancer-and-metastatic-disease
#20
REVIEW
Shih-Ying Wu, Kounosuke Watabe
Malignant brain tumors and brain metastases are highly aggressive diseases that are often resistant to treatment. Consequently, the current prognosis of patients with brain tumors and metastases is dismal. Activated microglia and macrophages are often observed in close proximity to or within the malignant tumor masses, suggesting that microglia/macrophages play an important role in brain tumor progression. Microglia, being resident macrophages of the central nervous system, form a major component of the brain immune system...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
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