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platelet activation,cancer

Jennifer H Shepherd, Daniel Howard, Amie K Waller, Holly Rebecca Foster, Annett Muller, Thomas Moreau, Amanda L Evans, Meera Arumugam, Guénaëlle Bouët Chalon, Eleonora Vriend, Natalia Davidenko, Cedric Ghevaert, Serena M Best, Ruth E Cameron
Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells...
August 8, 2018: Biomaterials
Preeti Kanikarla-Marie, Scott Kopetz, Ernest T Hawk, Steven W Millward, Anil K Sood, Paolo Gresele, Michael Overman, Kenneth Honn, David G Menter
Platelets can serve as "first responders" in cancer and metastasis. This is partly due to bioactive lipid metabolism that drives both platelet and cancer biology. The two primary eicosanoid metabolites that maintain platelet rapid response homeostasis are prostacyclin made by endothelial cells that inhibits platelet function, which is counterbalanced by thromboxane produced by platelets during activation, aggregation, and platelet recruitment. Both of these arachidonic acid metabolites are inherently unstable due to their chemical structure...
August 15, 2018: Cancer Metastasis Reviews
Zi-Qi Jin, Jian Hao, Xue Yang, Jing-Hua He, Jing Liang, Jin-Wei Yuan, Yu Mao, Dan Liu, Rui Cao, Xiong-Zhi Wu, Xin Li, Dan Chen
Cucurbitacin B (Cu B), a tetracyclic triterpenoid derived from Trichosanthes kirilowii Maxim, exhibits anticancer effects against various types of tumor. Higenamine, isolated from Radix Aconiti Lateralis Preparata, has been used as a dietary supplement for regulating metabolic function. The present study suggested that higenamine enhances Cu B-induced cytotoxicity in breast cancer cells and in vivo. Network pharmacology analysis was used to identify the possible mechanism of action. Cu B alone inhibited breast cancer cell growth, induced apoptosis, and arrested the cell cycle in the G2/M phase...
August 6, 2018: Oncology Reports
Wenhu Zhang, Shaozhuang Liu, Hanxiang Zhan, Zhibo Yan, Guangyong Zhang
The present study aimed to investigate the key pathways and genes associated with gastric adenocarcinoma via transcriptome sequencing. Five pairs of gastric adenocarcinoma tissue and normal tumor‑adjacent tissue were harvested. After sequencing, raw data were processed and differentially expressed genes (DEGs) between tumor and control groups were screened, followed by functional enrichment analysis and gene clustering analysis. The effect of DEGs on patient prognosis was analyzed on the basis of the survival data from gastric adenocarcinoma patients in The Cancer Genome Atlas database...
August 9, 2018: Molecular Medicine Reports
Hojjat Naderi-Meshkin, Naghmeh Ahmadiankia
One of the major obstacles in achieving a successful stem cell therapy is insufficient homing of transplanted cells. To overcome this obstacle, understanding the underlying mechanisms of stem cell homing is of obvious importance. Central to this review is the concept that cancer metastasis can be viewed as a role model to build up a comprehensive concept of stem cell homing. In this novel perspective, the prosurvival choices of the cancerous cells in the bloodstream, their arrest, extravasation, and proliferation at the secondary site can be exploited in favor of targeted stem cell homing...
August 13, 2018: Journal of Cellular Physiology
Konstantinos Syrigos, Dimitra Grapsa, Rabiatou Sangare, Ilias Evmorfiadis, Annette K Larsen, Patrick Van Dreden, Paraskevi Boura, Andriani Charpidou, Elias Kotteas, Theodoros N Sergentanis, Ismail Elalamy, Anna Falanga, Grigoris T Gerotziafas
BACKGROUND: The aim of this prospective study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE). SUBJECTS, MATERIALS, AND METHODS: One hundred fifty ambulatory patients with lung adenocarcinoma were prospectively enrolled. Thrombin generation, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P-selectin, and heparanase levels were assessed in platelet-poor plasma at inclusion (baseline) and at the end of the third chemotherapy cycle (third chemotherapy)...
August 13, 2018: Oncologist
T E Warkentin
Heparin-induced thrombocytopenia (HIT) is an acquired immune-mediated hypercoagulability state strongly associated with thrombosis. During the 1970s and 1980s, the prevailing concept was that HIT was associated only with arterial thrombosis, through its unique pathogenesis via heparin-dependent, platelet-activating IgG antibodies. Yet, in 1990, when I began to encounter HIT in my clinical practice, I found that most such patients developed symptomatic venous thrombosis. This historical sketch summarizes some of the research that challenged the dogma of HIT as a mainly arterial prothrombotic disorder...
August 12, 2018: Journal of Thrombosis and Haemostasis: JTH
Juan Jovel, Zhen Lin, Sandra O'keefe, Steven Willows, Weiwei Wang, Guangzhi Zhang, Jordan Patterson, Carlos Moctezuma-Velázquez, David J Kelvin, Gane Ka-Shu Wong, Andrew L Mason
Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low-pass sequencing data, and a set of 56 cancer-related genes were screened using an oncology panel assay...
August 2018: Hepatology Communications
Ping Zhang, Ying Chen, Tao Zhang, Jiang Zhu, Lei Zhao, Jianshuang Li, Guangzhi Wang, Yongchun Li, Shuchang Xu, Ake Nilsson, Rui-Dong Duan
Intestinal alkaline sphingomyelinase (alk-SMase) cleaves phosphocholine from sphingomyelin, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4-5 fold enhanced in alk-SMase knockout mice. Here we further studied pathogenesis of colitis induced by dextran sulfate sodium (DSS) in wild type (WT) and the knockout mice. Comparing with WT mice, knockout mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury...
August 7, 2018: Journal of Lipid Research
Robert J Canter, William J Murphy
Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers...
August 7, 2018: Journal for Immunotherapy of Cancer
Izabela Grzegorczyk-Karolak, Bogdan Kontek, Renata Kontek, Halina Wysokińska, Beata Olas
BACKGROUND: It is widely known that reactive oxygen species (ROS) can cause oxidative damage in cells and have been linked to the pathogenesis of oxidative diseases, such as atherosclerosis, ischemia, neurodegenerative disease, diabetes, or cancer. Recently, much attention has been focused on preventive strategies for oxidative stress and related diseases. Plants represent a source of bioactive compounds whose antioxidant activity may be useful in protecting against pro-oxidative reactions...
August 7, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Kun Wu, Jing-Shi Lei, Yuan-Yuan Mao, Wei Cao, Zhen-Hu Ren, Han-Jiang Wu
PURPOSE: Studies on coagulation parameters (including activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen [FIB], platelet count, and D-dimer) in flap compromise are limited. The aim of the present study was to compare coagulation parameter variables in patients with and without flap compromise. MATERIALS AND METHODS: In this retrospective cohort study, patients were recruited from the Department of Oral and Maxillofacial Surgery at the Second Xiangya Hospital (Changsha, Hunan, China) from July 2016 through July 2017...
July 11, 2018: Journal of Oral and Maxillofacial Surgery
Alexander Y Tsygankov
UBASH3/STS/TULA is a novel two-member family, which exerts several key regulatory effects in multiple cell types. UBASH3B/STS-1/TULA-2 is a highly active protein tyrosine phosphatase; its major target appears to be a specific regulatory site of protein tyrosine kinases of the Syk family, dephosphorylation of which inhibits Syk and Zap-70 kinases and suppresses receptor signaling mediated by these kinases. UBASH3A/STS-2/TULA exhibits substantial homology to UBASH3B/STS-1/TULA-2, but possesses only a small fraction of phosphatase activity of UBASH3B/STS-1/TULA-2, and thus, its regulatory effect may be based also on the phosphatase-independent mechanisms...
August 4, 2018: Journal of Cellular Physiology
Marta Smeda, Anna Kieronska, Mateusz G Adamski, Bartosz Proniewski, Magdalena Sternak, Tasnim Mohaissen, Kamil Przyborowski, Katarzyna Derszniak, Dawid Kaczor, Marta Stojak, Elzbieta Buczek, Agnieszka Jasztal, Joanna Wietrzyk, Stefan Chlopicki
BACKGROUND: Mesenchymal transformation of pulmonary endothelial cells contributes to the formation of a metastatic microenvironment, but it is not known whether this precedes or follows early metastasis formation. In the present work, we characterize the development of nitric oxide (NO) deficiency and markers of endothelial-mesenchymal transition (EndMT) in the lung in relation to the progression of 4T1 metastatic breast cancer injected orthotopically in mice. METHODS: NO production, endothelial nitric oxide synthase (eNOS) phosphorylation status, markers of EndMT in the lung, pulmonary endothelium permeability, and platelet activation/reactivity were analyzed in relation to the progression of 4T1 breast cancer metastasis to the lung, as well as to lung tissue remodeling, 1-5 weeks after 4T1 cancer cell inoculation in Balb/c mice...
August 3, 2018: Breast Cancer Research: BCR
Annalisa Bruno, Melania Dovizio, Stefania Tacconelli, Annalisa Contursi, Patrizia Ballerini, Paola Patrignani
Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination...
July 31, 2018: Cancers
Yu Miyama, Teppei Morikawa, Jimpei Miyakawa, Yuichi Koyama, Taketo Kawai, Haruki Kume, Masashi Fukayama
Programmed cell death ligand-1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) that negatively regulates T-cell activation and plays a crucial role in suppressing anti-tumor host immunity. Although PD-L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD-L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD-L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD-L1 might vary according to platelet count...
July 31, 2018: Cancer Medicine
Y-H Wang, H Qiu, X-L He, X-W Sun
OBJECTIVE: We aimed at analyzing the efficacy of low molecular heparin in the prevention of venous thromboembolism (VTE) after resection of primary liver cancer and at exploring the correlation of VTE with P-selectin (CD62P), lysosomal granule glycoprotein (CD63), platelet activating factor (PAF) and plasma D-dimer (D-D). PATIENTS AND METHODS: A total of 233 patients treated with primary liver cancer resection in our hospital from February 2014 to October 2016 were enrolled in this study...
July 2018: European Review for Medical and Pharmacological Sciences
Gilda Varricchi, Antonio Pecoraro, Giancarlo Marone, Gjada Criscuolo, Giuseppe Spadaro, Arturo Genovese, Gianni Marone
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine originally isolated from a murine thymic stromal cell line. TSLP exerts its biological effects by binding to a high-affinity heteromeric complex composed of thymic stromal lymphopoietin receptor chain and IL-7Rα. TSLP is primarily expressed by activated lung and intestinal epithelial cells, keratinocytes, and fibroblasts. However, dendritic cells (DCs), mast cells, and presumably other immune cells can also produce TSLP. Different groups of investigators have demonstrated the existence of two variants for TSLP in human tissues: the main isoform expressed in steady state is the short form (sf TSLP), which plays a homeostatic role, whereas the long form (lfTSLP) is upregulated in inflammatory conditions...
2018: Frontiers in Immunology
Hong Li, Manuel Zeitelhofer, Ingrid Nilsson, Xicong Liu, Laura Allan, Benjamin Gloria, Angelo Perani, Carmel Murone, Bruno Catimel, A Munro Neville, Fiona E Scott, Andrew M Scott, Ulf Eriksson
PDGF-CC is a member of the platelet-derived growth factor (PDGF) family that stimulates PDGFRα phosphorylation and thereby activates intracellular signalling events essential for development but also in cancer, fibrosis and neuropathologies involving blood-brain barrier (BBB) disruption. In order to elucidate the biological and pathological role(s) of PDGF-CC signalling, we have generated high affinity neutralizing monoclonal antibodies (mAbs) recognizing human PDGF-CC. We determined the complementarity determining regions (CDRs) of the selected clones, and mapped the binding epitope for clone 6B3...
2018: PloS One
Tsutomu Shimura, Megumi Sasatani, Hidehiko Kawai, Kenji Kamiya, Junya Kobayashi, Kenshi Komatsu, Naoki Kunugita
Fibroblasts are a key stromal cell in the tumor microenvironment (TME) and promote tumor growth via release of various growth factors. Stromal fibroblasts in cancer, called cancer-associated fibroblasts (CAFs), are related to myofibroblasts, an activated form of fibroblast. While investigating the role of stroma fibroblasts on radiation-related carcinogenesis, it was observed following long-term fractionated radiation (FR) that the morphology of human diploid fibroblasts changed from smaller spindle shapes to larger flat shapes...
July 24, 2018: Molecular Cancer Research: MCR
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