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Tumor dormancy

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https://www.readbyqxmd.com/read/29302774/suppression-of-metastasis-by-primary-tumor-and-acceleration-of-metastasis-following-primary-tumor-resection-a-natural-law
#1
Leonid Hanin, Jason Rose
We study metastatic cancer progression through an extremely general individual-patient mathematical model that is rooted in the contemporary understanding of the underlying biomedical processes yet is essentially free of specific biological assumptions of mechanistic nature. The model accounts for primary tumor growth and resection, shedding of metastases off the primary tumor and their selection, dormancy and growth in a given secondary site. However, functional parameters descriptive of these processes are assumed to be essentially arbitrary...
January 4, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29299114/stromal-cell-extracellular-vesicular-cargo-mediated-regulation-of-breast-cancer-cell-metastasis-via-ubiquitin-conjugating-enzyme-e2-n-pathway
#2
Krishna C Vallabhaneni, Patrice Penfornis, Fei Xing, Yoni Hassler, Kristen V Adams, Yin-Yuan Mo, Kounosuke Watabe, Radhika Pochampally
Mesenchymal stromal cells (hMSCs) have been used to understand the stromal cell properties in solid tumors because of their ablity to differentiate into most cell types. We investigated the role of EVs from hMSCs (hMSC-EVs) in breast cancer metastasis using MDA-MB-231 parental cell line and organotropic sub-lines. We demonstrated that hMSC-EVs significantly suppressed the metastatic potential of the parental cell line when compared to their organotropic sublines. hMSC-EVs induce dormancy in the parental cell line but not in their organotropic sub-lines and miR-205 and miR-31 from EV cargo played a role...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296224/dormant-glioblastoma-cells-acquire-stem-cell-characteristics-and-are-differentially-affected-by-temozolomide-and-at101-treatment
#3
Vivian Adamski, Annika Hempelmann, Charlotte Flüh, Ralph Lucius, Michael Synowitz, Kirsten Hattermann, Janka Held-Feindt
Cellular dormancy is defined as a state in which cells enter quiescence driven by intrinsic or extrinsic factors, and striking parallels exist between the concept of cellular dormancy in malignancies and the cancer stem cell theory. We showed now that the proven dormancy markers insulin-like growth factor-binding protein 5, ephrin receptor A5 and histone cluster 1 H2B family member K were expressed in human glioblastomas in situ, were located in single tumor cells, and could be co-stained with each other and with the stem cell markers krüppel-like factor 4, octamer binding transcription factor 4 and sex determining region Y-box 2...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29229606/coactivation-of-estrogen-receptor-and-ikk-%C3%AE-induces-a-dormant-metastatic-phenotype-in-er-positive-breast-cancer
#4
Lamiaa El-Shennawy, Oleksii Dubrovskyi, Irida Kastrati, Jeanne M Danes, Yiqun Zhang, Herbert E Whiteley, Chad J Creighton, Jonna Frasor
A growing body of evidence suggests that the inflammatory NFκB pathway is associated with the progression of ER+ tumors to more aggressive stages. However, it is unknown whether NFκB is a driver or a consequence of aggressive ER+ disease. To investigate this question, we developed breast cancer cell lines expressing an inducible, constitutively active form of IκB kinase β (CA-IKKβ), a key kinase in the canonical NFκB pathway. We found that CA-IKKβ blocked E2-dependent cell proliferation in vitro and tumor growth in vivo in a reversible manner, suggesting that IKKβ may contribute to tumor dormancy and recurrence of ER+ disease...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#5
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29198586/metastases-of-malignant-neoplasms-historical-biological-clinical-considerations
#6
REVIEW
Mark R Wick
The metastasis of neoplastic cells from their site of origin to distant anatomic locations continues to be the principal cause of death from malignant tumors, and that fact has been recognized by physicians for over a century. After the work done by Halsted in the treatment of breast cancer in the 1880s, accepted surgical canon held that metastasis occurred in a linear fashion, with centrifugal "growth in continuity" from the primary neoplasm that first involved regional lymph nodes. Those structures were considered to then be the sources of more distant, visceral metastases...
November 24, 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/29192415/dna-methyltransferase-inhibitors-influence-on-the-diras3-and-stat3-expression-and-in-vitro-migration-of-ovarian-and-breast-cancer-cells
#7
Ewa Maria Nowak, Marta Poczęta, Dominik Bieg, Ilona Bednarek
OBJECTIVES: Downregulation of DIRAS3 (DIRAS family, GTP-binding Ras-like 3) is related to ovarian and breast cancer progression. A possible mechanism that silences this gene is the promoter region DNA methylation. The potential reversibility of this epigenetic mechanism makes it more attractive candidate for new mode of cancer treatment. DIRAS3 regulates cell cycle, tumor dormancy and inhibits cancer cell growth and motility, all of which may indirectly depend on interaction with STAT3 (Signal Transducer and Activator of Transcription 3) classified as a potential oncogene...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/29167804/extracellular-vesicle-mediated-transport-of-non-coding-rnas-between-stem-cells-and-cancer-cells-implications-in-tumor-progression-and-therapeutic-resistance
#8
REVIEW
Muhammad Nawaz
Recent years have witnessed intensive progress in studying extracellular vesicles (EVs), both for understanding their basic biology and contribution to variety of diseases, biomarker discovery, and their potential as gene delivery vectors and source of innovative therapies. As such, stem cell-derived EVs have contributed significant knowledge which led to the development of cell-free therapies in regenerative medicine. Although, the role of stem cell-derived EVs in maintaining stemness, differentiation and repairing tissue injuries is relatively well-understood; however, knowledge about the contribution of stem cell-derived EVs in cancer progression is just emerging...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29138574/cancer-cell-dormancy-mechanisms-and-implications-of-cancer-recurrence-and-metastasis
#9
REVIEW
Xiao-Lei Gao, Mei Zhang, Ya-Ling Tang, Xin-Hua Liang
More recently, disease metastasis and relapse in many cancer patients several years (even some decades) after surgical remission are regarded as tumor dormancy. However, the knowledge of this phenomenon is cripplingly limited. Substantial quantities of reviews have summarized three main potential models that can be put forth to explain such process, including angiogenic dormancy, immunologic dormancy, and cellular dormancy. In this review, newly uncovered mechanisms governing cancer cell dormancy are discussed, with an emphasis on the cross talk between dormant cancer cells and their microenvironments...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29137633/bi-directional-exosome-driven-intercommunication-between-the-hepatic-niche-and-cancer-cells
#10
Nikolina Dioufa, Amanda M Clark, Bo Ma, Colin H Beckwitt, Alan Wells
BACKGROUND: Our understanding of the multiple roles exosomes play during tumor progression is still very poor and the contribution of the normal tissue derived exosomes in distant seeding and tumor outgrowth has also not been widely appreciated. METHODS: Using our all-human liver microphysiological system (MPS) platform as a model to closely recapitulate the early metastatic events, we isolated exosomes from both tumor cells and liver microenvironment. RESULTS: We observed that while priming of the hepatic niche (HepN) with MDA-231 breast cancer derived exosomes facilitated seeding of the cancer cells in the liver, subsequent tumor outgrowth was diminished; this was consistent with increased entry into dormancy...
November 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29108332/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#11
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/m(2), d1 plus oral cyclophosphamide 50 mg daily) or T alone...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108242/characterization-and-functional-analysis-of-a-slow-cycling-subpopulation-in-colorectal-cancer-enriched-by-cell-cycle-inducer-combined-chemotherapy
#12
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...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101110/the-biology-of-bone-metastasis
#13
Mark Esposito, Theresa Guise, Yibin Kang
Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29020635/human-organ-chip-models-recapitulate-orthotopic-lung-cancer-growth-therapeutic-responses-and-tumor-dormancy-in%C3%A2-vitro
#14
Bryan A Hassell, Girija Goyal, Esak Lee, Alexandra Sontheimer-Phelps, Oren Levy, Christopher S Chen, Donald E Ingber
Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy observed in human patients in vivo. Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28868144/inhibition-of-il-17a-by-secukinumab-shows-no-evidence-of-increased-mycobacterium-tuberculosis-infections
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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