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Tumor priming

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https://www.readbyqxmd.com/read/28101375/aurora-a-promotes-the-establishment-of-spindle-assembly-checkpoint-by-priming-the-haspin-aurora-b-feedback-loop-in-late-g2-phase
#1
Fazhi Yu, Ya Jiang, Lucy Lu, Mimi Cao, Yulong Qiao, Xing Liu, Dan Liu, Terry Van Dyke, Fangwei Wang, Xuebiao Yao, Jing Guo, Zhenye Yang
Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28097640/priming-increases-the-anti-tumor-effect-and-therapeutic-window-of-177-lu-octreotate-in-nude-mice-bearing-human-small-intestine-neuroendocrine-tumor-got1
#2
Johanna Dalmo, Johan Spetz, Mikael Montelius, Britta Langen, Yvonne Arvidsson, Henrik Johansson, Toshima Z Parris, Khalil Helou, Bo Wängberg, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-[DOTA(0), Tyr(3)]-octreotate ((177)Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase (177)Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a (177)Lu-octreotate priming dose followed 24 h later by a second injection of (177)Lu-octreotate compared to a single administration of (177)Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28096297/frontline-science-tumor-necrosis-factor-%C3%AE-stimulation-and-priming-of-human-neutrophil-granule-exocytosis
#3
Kenneth R McLeish, Michael L Merchant, T Michael Creed, Shweta Tandon, Michelle T Barati, Silvia M Uriarte, Richard A Ward
Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28090647/the-multifaceted-role-of-extracellular-vesicles-in-metastasis-priming-the-soil-for-seeding
#4
REVIEW
Brunna Dos Anjos Pultz, Felipe Andrés Cordero da Luz, Sara Socorro Faria, Leandro Peixoto Ferreira de Souza, Paula Cristina Brígido Tavares, Vivian Alonso Goulart, Wagner Fontes, Luiz Ricardo Goulart, Marcelo José Barbosa Silva
Extracellular vesicles (EVs), including exosomes, play a key role in inter and intracellular communication, promoting the proliferation and invasion of recipient cells to support tumor growth and metastasis. Metastasis comprises multiple steps that first include the detachment of tumor cells through epithelial to mesenchymal transition (EMT), allowing the physical dissemination to distant organs. Thereafter, cancer-derived exosomes are still critical components for preparing the tumor microenvironment by (i) enabling tumor cells to escape from the immunological surveillance and (ii) arranging the pre-metastatic site for the engraftment of detached cancer cells...
January 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28088700/chlorogenic-acid-ameliorated-concanavalin-a-induced-hepatitis-by-suppression-of-toll-like-receptor-4-signaling-in-mice
#5
Yinglin Yuan, Xia Gong, Li Zhang, Rong Jiang, Junxia Yang, Bin Wang, Jingyuan Wan
Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4(+) T lymphocytes in Con A-primed mice...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28069800/label-free-raman-spectroscopy-detects-stromal-adaptations-in-premetastatic-lungs-primed-by-breast-cancer
#6
Santosh Kumar Paidi, Asif Rizwan, Chao Zheng, Menglin Cheng, Kristine Glunde, Ishan Barman
Recent advances in animal modeling, imaging technology, and functional genomics have permitted precise molecular observations of the metastatic process. However, a comprehensive understanding of the premetastatic niche remains elusive, owing to the limited tools that can map subtle differences in molecular mediators in organ-specific microenvironments. Here, we report the ability to detect premetastatic changes in the lung microenvironment, in response to primary breast tumors, using a combination of metastatic mouse models, Raman spectroscopy, and multivariate analysis of consistent patterns in molecular expression...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28068936/retrospective-study-of-ras-pik3ca-braf-tumor-mutations-as-predictors-of-response-to-first-line-chemotherapy-with-bevacizumab-in-metastatic-colorectal-cancer-patients
#7
Izuma Nakayama, Eiji Shinozaki, Tomohiro Matsushima, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Masato Ozaka, Daisuke Takahari, Mitsukuni Suenaga, Keisho Chin, Nobuyuki Mizunuma, Kensei Yamaguchi
BACKGROUND: After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28064387/the-role-of-histone-modifications-and-telomere-alterations-in-the-pathogenesis-of-diffuse-gliomas-in-adults-and-children
#8
REVIEW
Julieann Lee, D A Solomon, Tarik Tihan
Genetic profiling is an increasingly useful tool for sub-classification of gliomas in adults and children. Specific gene mutations, structural rearrangements, DNA methylation patterns, and gene expression profiles are now recognized to define molecular subgroups of gliomas that arise in distinct anatomic locations and patient age groups, and also provide a better prediction of clinical outcomes for glioma patients compared to histologic assessment alone. Understanding the role of these distinctive genetic alterations in gliomagenesis is also important for the development of potential targeted therapeutic interventions...
January 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28053544/nab-paclitaxel-as-a-potential-partner-with-checkpoint-inhibitors-in-solid-tumors
#9
REVIEW
Hatem H Soliman
Tumors recognized by the host immune system are associated with better survival. However, the immune system is often suppressed in patients with established tumor burden. Stimulating the immune system to detect and kill tumor cells has been a challenge in cancer therapy for some time. Recently, novel cancer immunotherapies, such as immune checkpoint inhibitors, monoclonal antibodies, and vaccine therapies, have emerged as promising therapeutic approaches for many solid tumors. However, for some tumors, immunotherapy alone has not provided significant benefits, and some may even be fully resistant to immunotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28042950/ccl24-contributes-to-hcc-malignancy-via-rhob-vegfa-vegfr2-angiogenesis-pathway-and-indicates-poor-prognosis
#10
Lei Jin, Wei-Ren Liu, Meng-Xin Tian, Xi-Fei Jiang, Han Wang, Pei-Yun Zhou, Zhen-Bin Ding, Yuan-Fei Peng, Zhi Dai, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Ying-Hong Shi
CCL24 is one chemotactic factor extensively studied in airway inflammation and colorectal cancer but less studied in hepatocellular carcinoma (HCC) retrospectively. So HCC tissue microarray (TMA) was used to estimate relationship between CCL24 and prognosis, cell experiments were conducted to study its influence for HCC cell biological behavior. CCL24 was injected to nude mice to monitor tumor formation and pulmonary metastasis; qRT-PCR, western blot and Immunohistochemistry were used to explore potential mechanism...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039455/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#11
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, R Chris Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039445/aromatase-inhibitor-induced-bone-loss-increases-the-progression-of-estrogen-receptor-negative-breast-cancer-in-bone-and-exacerbates-muscle-weakness-in-vivo
#12
Laura E Wright, Ahmed A Harhash, Wende M Kozlow, David L Waning, Jenna N Regan, Yun She, Sutha K John, Sreemala Murthy, Maryla Niewolna, Andrew R Marks, Khalid S Mohammad, Theresa A Guise
Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let)...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027584/il6-dependent-genomic-instability-heralds-accelerated-carcinogenesis-following-liver-regeneration-on-a-background-of-chronic-hepatitis
#13
Tali Lanton, Anat Shriki, Yael Nechemia-Arbely, Rinat Abramovitch, Orr Levkovitch, Revital Adar, Nofar Rosenberg, Mor Paldor, Daniel Goldenberg, Amir Sonnenblick, Amnon Peled, Stefan Rose-John, Eithan Galun, Jonathan H Axelrod
: Liver cancer, which typically develops on a background of chronic liver inflammation, is now the second leading cause of cancer mortality worldwide. For these patients surgical resection is a principal treatment modality that offers a chance of prolonged survival. However, tumor recurrence after resection, the mechanisms of which remain obscure, markedly limits the long-term survival of these patients. We have previously shown that partial hepatectomy (PH) in Mdr2 knockout (Mdr2(-/-) ) mice, a model of chronic inflammation-associated liver cancer, significantly accelerates hepatocarcinogenesis...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28018989/the-intersection-of-radiotherapy-and-immunotherapy-mechanisms-and-clinical-implications
#14
Michael Spiotto, Yang-Xin Fu, Ralph R Weichselbaum
By inducing DNA damage, radiotherapy both reduces tumor burden and enhances anti-tumor immunity. Here, we will review the mechanisms by which radiation induces anti-tumor immune responses that can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the NF-κB and the Type I interferon response pathways to induce expression of pro-inflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses...
September 2016: Science Immunology
https://www.readbyqxmd.com/read/27999742/reprogramming-of-tlr7-signaling-enhances-antitumor-nk-and-cytotoxic-t-cell-responses
#15
Christian Hotz, Marina Treinies, Ines Mottas, Laurin C Rötzer, Anne Oberson, Lorenzo Spagnuolo, Maurizio Perdicchio, Thibaud Spinetti, Tina Herbst, Carole Bourquin
Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly(I:C) that mimics virally induced immune activation...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999204/mesothelin-targeted-immunotoxin-rg7787-has-synergistic-anti-tumor-activity-when-combined-with-taxanes
#16
Emily Kolyvas, Michael Rudloff, Marianne Poruchynsky, Rebekah Landsman, Kevin Hollevoet, David Venzon, Christine Alewine
Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994166/intratumoral-delivery-of-immunotherapy-act-locally-think-globally
#17
REVIEW
M Angela Aznar, Nicola Tinari, Antonio J Rullán, Alfonso R Sánchez-Paulete, María E Rodriguez-Ruiz, Ignacio Melero
Immune mechanisms have evolved to cope with local entry of microbes acting in a confined fashion but eventually inducing systemic immune memory. Indeed, in situ delivery of a number of agents into tumors can mimic in the malignant tissue the phenomena that control intracellular infection leading to the killing of infected cells. Vascular endothelium activation and lymphocyte attraction, together with dendritic cell-mediated cross-priming, are the key elements. Intratumoral therapy with pathogen-associated molecular patterns or recombinant viruses is being tested in the clinic...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27993616/quantitative-multi-target-rna-profiling-in-epstein-barr-virus-infected-tumor-cells
#18
A E Greijer, O Ramayanti, S A W M Verkuijlen, Z Novalić, H Juwana, J M Middeldorp
Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts...
December 16, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27992856/induction-of-fibroblast-senescence-generates-a-non-fibrogenic-myofibroblast-phenotype-that-differentially-impacts-on-cancer-prognosis
#19
Massimiliano Mellone, Christopher J Hanley, Steve Thirdborough, Toby Mellows, Edwin Garcia, Jeongmin Woo, Joanne Tod, Steve Frampton, Veronika Jenei, Karwan A Moutasim, Tasnuva D Kabir, Peter A Brennan, Giulia Venturi, Kirsty Ford, Nicolas Herranz, Kue Peng Lim, James Clarke, Daniel W Lambert, Stephen S Prime, Timothy J Underwood, Pandurangan Vijayanand, Kevin W Eliceiri, Christopher Woelk, Emma V King, Jesus Gil, Christian H Ottensmeier, Gareth J Thomas
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling...
December 15, 2016: Aging
https://www.readbyqxmd.com/read/27991524/macrophages-enhance-migration-in-inflammatory-breast-cancer-cells-via-rhoc-gtpase-signaling
#20
Steven G Allen, Yu-Chih Chen, Julie M Madden, Chelsea L Fournier, Megan A Altemus, Ayse B Hiziroglu, Yu-Heng Cheng, Zhi Fen Wu, Liwei Bao, Joel A Yates, Euisik Yoon, Sofia D Merajver
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC). Genetic profiling studies have been conducted to differentiate IBC from nIBC, but no IBC cancer-cell-specific gene signature has been identified. We hypothesized that a tumor-extrinsic factor, notably tumor-associated macrophages, promotes and contributes to IBC's extreme metastatic phenotype...
December 19, 2016: Scientific Reports
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