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Tumor priming

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https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#1
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#2
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#3
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29769201/in-vitro-priming-of-adoptively-transferred-t-cells-with-a-ror%C3%AE-agonist-confers-durable-memory-and-stemness-in-vivo
#4
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29756328/serum-derived-carcinoembryonic-antigen-cea-activates-fibroblasts-to-induce-a-local-re-modeling-of-the-extracellular-matrix-that-favors-the-engraftment-of-cea-expressing-tumor-cells
#5
Aws Abdul-Wahid, Marzena Cydzik, Nicholas W Fischer, Aaron Prodeus, John E Shively, Anne Martel, Samira Alminawi, Zeina Ghorab, Neil L Berinstein, Jean Gariépy
Elevated levels of the carcinoembryonic antigen (CEA; CEACAM5) in the serum of colorectal cancer (CRC) patients represent a clinical biomarker that correlates with disease recurrence. However, a mechanistic role for soluble CEA (sCEA) in tumor progression and metastasis remains to be established. In this study, we report that sCEA acts as a paracrine factor, activating human fibroblasts by signalling through both the STAT3 and AKT1-mTORC1 pathways, promoting their transition to a cancer-associated fibroblast (CaF) phenotype...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29753032/enhancement-of-cutaneous-wound-healing-by-dsg2-augmentation-of-upar-secretion
#6
Felicia Cooper, Andrew M Overmiller, Anthony Loder, Donna M Brennan-Crispi, Kathleen P McGuinn, Molly R Marous, Theresa A Freeman, Natalia A Riobo-Del Galdo, Linda D Siracusa, James K Wahl, Mỹ G Mahoney
In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development...
May 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29752716/low-dose-irradiated-mesenchymal-stromal-cells-break-tumor-defensive-properties-in-vivo
#7
Francesca Romana Stefani, Sofia Eberstål, Stefano Vergani, Trine A Kristiansen, Johan Bengzon
Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies to overcome tumor resistance are mainly represented by multi-targeted approaches, and cell vector-based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow-derived mesenchymal stromal cells (MSCs), when primed with low-dose irradiation (irMSCs), undergo changes in their immunogenic and angiogenic capacity and acquire anti-tumoral properties in a mouse model of glioblastoma (GBM)...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752262/cd4-t-cell-mediated-rejection-of-mhc-class-ii-positive-tumor-cells-is-dependent-on-antigen-secretion-and-indirect-presentation-on-host-apcs
#8
Ole Audun Werner Haabeth, Marte Fauskanger, Melanie Manzke, Katrin U Lundin, Alexandre Corthay, Bjarne Bogen, Anders Aune Tveita
Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection...
May 11, 2018: Cancer Research
https://www.readbyqxmd.com/read/29751609/pterostilbene-and-4-methoxyresveratrol-inhibited-lipopolysaccharide-induced-inflammatory-response-in-raw264-7-macrophages
#9
Yun Yao, Kehai Liu, Yueliang Zhao, Xiaoqian Hu, Mingfu Wang
Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA expression. Moreover, both of them inhibited LPS-induced mRNA expression of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and IL-1β, and tumor necrosis factor α (TNF-α), and attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 phosphorylation...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29740793/immune-checkpoint-receptors-homeostatic-regulators-of-immunity
#10
REVIEW
Antonio Riva, Shilpa Chokshi
Alcoholic liver disease (ALD) is an escalating global problem accounting for more than 3 million deaths annually. Bacterial infections are diagnosed in 25-47% of hospitalized patients with cirrhosis and represent the most important trigger for acute decompensation, multi-organ failure, septic shock and death. Current guidelines recommend intensive antibiotic therapy, but this has led to the emergence of multi-drug resistant bacteria, which are associated with increased morbidity and mortality rates. As such, there is a pressing need to explore new paradigms for anti-infective therapy and host-directed immunomodulatory therapies are a promising approach...
May 8, 2018: Hepatology International
https://www.readbyqxmd.com/read/29735912/towards-resolving-the-pro-and-anti-tumor-effects-of-the-aryl-hydrocarbon-receptor
#11
Supraja Narasimhan, Elizabeth Stanford Zulick, Olga Novikov, Ashley J Parks, Jennifer J Schlezinger, Zhongyan Wang, Fabrice Laroche, Hui Feng, Francesca Mulas, Stefano Monti, David H Sherr
We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics. Molecular (siRNA, shRNA, AHR repressor, CRISPR-Cas9) and pharmacological (AHR inhibitors) approaches were used to confirm the hypothesis that AHR inhibition reduces human cancer cell invasion (irregular colony growth in 3D Matrigel cultures and Boyden chambers), migration (scratch wound assay) and metastasis (human cancer cell xenografts in zebrafish)...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29734804/a-novel-nanoparticle-formulation-derived-from-carboxymethyl-cellulose-polyethylene-glycol-and-cabazitaxel-for-chemotherapy-delivery-to-the-brain
#12
Joseph Bteich, Mark J Ernsting, Mohammed Z Mohammed, Taira Kiyota, Trevor McKee, Mohit Trikha, Henry Lowman, Kenneth K Sokoll
Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger-as opposed to smaller and/or actively transported-molecules to the brain is prime face a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects...
May 7, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29728623/specific-features-of-human-monocytes-activation-by-monophosphoryl-lipid-a
#13
Ryme Chentouh, Catherine Fitting, Jean-Marc Cavaillon
We deciphered the mechanisms of production of pro- and anti-inflammatory cytokines by adherent human blood mononuclear cells (PBMC) activated by lipopolysaccharide (LPS) or monophosphoryl lipid A (MPLA). Both LPS and MPLA induced tumor necrosis factor (TNF) production proved to be dependent on the production of interleukin-1β (IL-1β). Of note, MPLA induced IL-1β release in human adherent PBMCs whereas MPLA was previously reported to not induce this cytokine in murine cells. Both LPS and MPLA stimulatory effects were inhibited by Toll-like receptor-4 (TLR4) antagonists...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29725354/src-is-a-prime-target-inhibited-by-celtis-choseniana-methanol-extract-in-its-anti-inflammatory-action
#14
Han Gyung Kim, Subin Choi, Jongsung Lee, Yo Han Hong, Deok Jeong, Keejung Yoon, Deok Hyo Yoon, Gi-Ho Sung, Seungihm Lee, Suntaek Hong, Young-Su Yi, Jong-Hoon Kim, Jae Youl Cho
Celtis choseniana is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although Celtis choseniana has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti-inflammatory activity. Therefore, the present study explored an anti-inflammatory effect and its underlying molecular mechanism using Celtis choseniana methanol extract (Cc-ME) in macrophage-mediated inflammatory responses. In vitro anti-inflammatory activity of Cc-ME was evaluated using RAW264...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29721366/tnfa-and-il-2-armed-adenoviruses-enable-complete-responses-by-anti-pd-1-checkpoint-blockade
#15
V Cervera-Carrascon, M Siurala, J M Santos, R Havunen, S Tähtinen, P Karell, S Sorsa, A Kanerva, A Hemminki
Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29713453/anti-ctla-4-antibodies-in-cancer-immunotherapy-selective-depletion-of-intratumoral-regulatory-t-cells-or-checkpoint-blockade
#16
Fei Tang, Xuexiang Du, Mingyue Liu, Pan Zheng, Yang Liu
Antibodies to human CTLA-4 have been shown to induce long-lasting protection against melanoma. It is assumed that these antibodies cause tumor rejection by blocking negative signaling from the B7-CTLA-4 interactions to enhance priming of naïve T cells in the lymphoid organs. Recently, we reported that anti-CTLA-4 antibody Ipilimumab effectively induces tumor rejection in vivo although it blocks neither B7 transendocytosis by CTLA-4 nor CTLA-4 binding to immobilized or cell-associated B7. Using genetic model in which the anti-CTLA-4 antibodies are unable to engage more than 50% of CTLA-4, we demonstrated that saturating binding of CTLA-4 is not necessary for tumor rejection...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29709247/blocking-don-t-eat-me-signal-of-cd47-sirp%C3%AE-in-hematological-malignancies-an-in-depth-review
#17
REVIEW
Atlantis Russ, Anh B Hua, William R Montfort, Bushra Rahman, Irbaz Bin Riaz, Muhammad Umar Khalid, Jennifer S Carew, Steffan T Nawrocki, Daniel Persky, Faiz Anwer
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148...
April 14, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29706657/hypertonicity-enforced-bcl-2-addiction-unleashes-the-cytotoxic-potential-of-death-receptors
#18
Simon Sirtl, Gertrud Knoll, Dieu Thuy Trinh, Isabell Lang, Daniela Siegmund, Stefanie Gross, Beatrice Schuler-Thurner, Patrick Neubert, Jonathan Jantsch, Harald Wajant, Martin Ehrenschwender
Attempts to exploit the cytotoxic activity of death receptors (DR) for treating cancer have thus far been disappointing. DR activation in most malignant cells fails to trigger cell death and may even promote tumor growth by activating cell death-independent DR-associated signaling pathways. Overcoming apoptosis resistance is consequently a prerequisite for successful clinical exploitation of DR stimulation. Here we show that hyperosmotic stress in the tumor microenvironment unleashes the deadly potential of DRs by enforcing BCL-2 addiction of cancer cells...
April 30, 2018: Oncogene
https://www.readbyqxmd.com/read/29703078/advances-in-studies-of-aptamer-protein-targets-identification-using-chromatographic-approach
#19
Anna Drabik, Joanna Ner-Kluza, Przemyslaw Mielczarek, Laia Civit, Günter Mayer, Jerzy Silberring
Ever since the development of the process known as Systematic Evolution of Ligands by EXponential enrichment (SELEX) aptamers are widely used in variety of studies, including exploration of new diagnostic tools and discovery of new treatment methods. Aptamers abilities to bind to proteins with high affinity and specificity, often compared to antibodies, enable the search for potential cancer biomarkers and help to understand the mechanisms of cancerogenesis. The blind-spot of those investigations is usually the difficulty in selective extraction of targets attached to the aptamer...
April 27, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29700053/tk-inhibitor-pazopanib-primes-dcs-by-downregulation-of-the-%C3%AE-catenin-pathway
#20
Ilaria Grazia Zizzari, Chiara Napoletano, Andrea Botticelli, Salvatore Caponnetto, Fabio Calabrò, Alain Gelibter, Aurelia Rughetti, Ilary Ruscito, Hassan Rahimi, Ernesto Rossi, Giovanni Schinzari, Paolo Marchetti, Marianna Nuti
Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting, for example, the VEGF receptors in tumors and have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have also been proposed for treatment of mRCC with encouraging results. A better understanding of the activity of immune cells in mRCC, the immuneomodulatory effects of TKIs, and the characteristics defining patients most likely to benefit from various therapies will help optimize immunotherapeutic approaches...
April 26, 2018: Cancer Immunology Research
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