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platelet releasate

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https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#1
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28646118/direct-oral-anticoagulants-for-treatment-of-hit-update-of-hamilton-experience-and-literature-review
#2
Theodore E Warkentin, Menaka Pai, Lori-Ann Linkins
Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, Canada, since January 1, 2015 (when we completed our prospective rivaroxaban for HIT study) using rivaroxaban for serologically-confirmed HIT (4Ts score ≥4 points, PF4/heparin immunoassay-positive, serotonin-release assay positive). We also performed a literature review of HIT treatment using a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28645780/salvia-miltiorrhiza-bunge-danshen-extract-attenuates-permanent-cerebral-ischemia-through-inhibiting-platelet-activation-in-rats
#3
Yu-Xiang Fei, Si-Qi Wang, Li-Jian Yang, Yan-Ying Qiu, Yi-Ze Li, Wen-Yuan Liu, Tao Xi, Wei-Rong Fang, Yun-Man Li
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28645130/sustained-release-of-transforming-growth-factor-%C3%AE-1-from-platelet-rich-chondroitin-sulfate-glycosaminoglycan-gels
#4
Kate E Birdwhistell, Lohitash Karumbaiah, Samuel P Franklin
No abstract text is available yet for this article.
June 23, 2017: Journal of Knee Surgery
https://www.readbyqxmd.com/read/28642617/podoplanin-enhances-lung-cancer-cell-growth-in-vivo-by-inducing-platelet-aggregation
#5
Kenichi Miyata, Ai Takemoto, Sakae Okumura, Makoto Nishio, Naoya Fujita
Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638347/bile-acids-do-not-contribute-to-the-altered-calcium-homeostasis-of-platelets-from-rats-with-biliary-cirrhosis
#6
Paola Romecín, Esther G Navarro, M Clara Ortiz, David Iyú, Joaquín García-Estañ, Noemí M Atucha
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28638139/platelet-releasates-promote-the-proliferation-of-hepatocellular-carcinoma-cells-by-suppressing-the-expression-of-klf6
#7
Ao-Di He, Wen Xie, Wei Song, Yuan-Yuan Ma, Gang Liu, Ming-Lu Liang, Xing-Wen Da, Guang-Qiang Yao, Bi-Xiang Zhang, Cun-Ji Gao, Ji-Zhou Xiang, Zhang-Yin Ming
Platelets in the primary tumor microenvironment play crucial roles in the regulation of tumor progression, but the mechanisms underlying are poorly understood. Here, we report that platelet releasates exerted a proliferative effect on hepatocellular carcinoma (HCC) cells both in vitro and in vivo. This effect depended on a reduction of KLF6 expression in HCC cells. After incubation with either platelets or platelet granule contents, SMMC.7721 and HepG2 cells exhibited significant increases in proliferation and decreases in apoptosis...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637952/heat-shock-protein-72-promotes-platelet-aggregation-induced-by-various-platelet-activators-in-rats
#8
Hideaki Suzuki, Yuuko Kosuge, Koji Kobayashi, Yoshifumi Kurosaki, Naohito Ishii, Naoyoshi Aoyama, Kazuhiko Ishihara, Takafumi Ichikawa
Increase of thrombus in the coronary arteries is positively correlated with the level of heat-shock protein 72 (HSP72) in the blood of patients with acute myocardial infarction (AMI). Platelet aggregation participates in thrombus formation on ruptured plaque in AMI. In this study, we aimed to clarify the role of HSP72 in thrombus formation by evaluating the effects of HSP72 on platelet aggregation. Platelet aggregation activities were measured in platelet-rich plasma obtained from male Sprague-Dawley rats with or without the platelet activators, such as adenosine diphosphate (ADP), collagen, thrombin receptor-activating peptide-6 (TRAP-6), ristocetin, and arachidonic acid...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28635382/white-cell-and-platelet-content-affects-the-release-of-bioactive-factors-in-different-blood-derived-scaffolds
#9
S Cabaro, V D'Esposito, R Gasparro, F Borriello, F Granata, G Mosca, F Passaretti, J C Sammartino, F Riccitiello, F Beguinot, P Formisano, G Sammartino
Platelet-derived factors are biomaterials that might accelerate healing process in oral, maxillofacial, and several other applications. Release of specific factors by platelet concentrates is critical to achieving a successful outcome. Here, we have shown that platelet-rich fibrin (PRF) clots were beneficial sources of leukocytes, which may directly affect the release of chemokines and growth factors. When compared with the standard leukocyte-PRF (L-PRF), the experimental low-force modified procedure [defined as advanced-PRF (A-PRF)] entrapped the same content of viable leukocytes, released a similar amount of inflammatory cytokines, but secreted 3-, 1...
June 21, 2017: Platelets
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#10
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28625264/-suppressive-effect-of-corm-2-on-platelet-%C3%AE-granule-exocytosis-in-sepsis-via-snare-munc18b-complex-formation
#11
Mingfeng Zhuang, Bingwei Sun, Dadong Liu, Yuan Shi
OBJECTIVE: To investigate the suppressive effect of carbon monoxide-releasing molecule II (CORM-2) on LPS induced platelet α-granule exocytosis in sepsis via soluble N-ethylmaleimide-sensitive factor attached protein receptor/mammalian uncoordinated 18b (SNARE/Munc18b) complex formation. METHODS: Blood was collected from healthy volunteers' cubital vein, then platelets were isolated by differential centrifugation. Platelets were randomly divided into 5 groups. The control group did not undergo any treatment, the LPS group received 10 mg/L LPS simulation, the CORM-2 group and iCORM-2 group underwent LPS simulation and immediate administration of CORM-2 (10 μmol/L and 50 μmol/L) or iCORM-2 (50 μmol/L), respectively...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28623810/platelet-granule-release-is-associated-with-reactive-oxygen-species-generation-during-platelet-storage-a-direct-link-between-platelet-pro-inflammatory-and-oxidation-states
#12
Mehran Ghasemzadeh, Ehteramolsadat Hosseini
BACKGROUND: Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. MATERIAL AND METHOD: PRP-platelet concentrates were subjected to flowcytometry analysis to assess the expression of platelet activation marker, P-selectin and CD40L during storage...
June 10, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28622977/evolution-of-the-%C3%AE-2-adrenoreceptors-in-vertebrates-adra2d-is-absent-in-mammals-and-crocodiles
#13
Héctor A Céspedes, Kattina Zavala, Michael W Vandewege, Juan C Opazo
Evolutionary studies of genes that have been functionally characterized and whose variation has been associated with pathological conditions represent an opportunity to understand the genetic basis of pathologies. α2-Adrenoreceptors (ADRA2) are a class of G protein-coupled receptors that regulate several physiological processes including blood pressure, platelet aggregation, insulin secretion, lipolysis, and neurotransmitter release. This gene family has been extensively studied from a molecular/physiological perspective, yet much less is known about its evolutionary history...
June 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28622439/clinical-effectiveness-of-a-bayesian-algorithm-for-the-diagnosis-and-management-of-heparin-induced-thrombocytopenia
#14
Robert A Raschke, Tyler Gallo, Steven C Curry, Tonya Whiting, Angela Padilla-Jones, Theodore E Warkentin
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by anti-platelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have limitations. We previously developed a diagnostic algorithm for HIT that incorporated "four Ts" (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% CI: 0.93-1.00). OBJECTIVES: The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care...
June 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#15
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28618256/cigarette-smoke-regulates-calcium-independent-phospholipase-a2-metabolic-pathways-in-breast-cancer
#16
Shannon Kispert, Theresa Schwartz, Jane McHowat
Phospholipase A2 (PLA2)-dependent pathways are important in the regulation of cell proliferation, differentiation, motility, and immune responses, and can be dysregulated during tumor development and progression. We show herein, for the first time, that cigarette smoking leads to an increase in platelet-activating factor (PAF) content and PAF receptor expression in human breast cancer cells and tissue. PAF production could be abrogated in triple-negative breast cancer cells by inhibition of calcium-independent PLA2 (iPLA2)...
June 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28614785/drag-reducing-polymers-decrease-hepatic-injury-and-metastases-after-liver-ischemia-reperfusion
#17
Samer Tohme, Marina V Kameneva, Hamza O Yazdani, Vikas Sud, Julie Goswami, Patricia Loughran, Hai Huang, Richard L Simmons, Allan Tsung
INTRODUCTION: Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614734/multifunctional-magnetic-responsive-hydrogels-to-engineer-tendon-to-bone-interface
#18
Elsa D Silva, Pedro S Babo, Raquel Costa-Almeida, Rui M A Domingues, Bárbara B Mendes, Elvira Paz, Paulo Freitas, Márcia T Rodrigues, Pedro L Granja, Manuela E Gomes
Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel...
June 11, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28611774/epidemiology-mechanisms-and-diagnosis-of-drug-induced-anaphylaxis
#19
REVIEW
Maria Isabel Montañez, Cristobalina Mayorga, Gador Bogas, Esther Barrionuevo, Ruben Fernandez-Santamaria, Angela Martin-Serrano, Jose Julio Laguna, Maria José Torres, Tahia Diana Fernandez, Inmaculada Doña
Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators by mast cells and basophils. Although anaphylaxis is often under-communicated and thus underestimated, its incidence appears to have risen over recent decades. Drugs are among the most common triggers in adults, being analgesics and antibiotics the most common causal agents. Anaphylaxis can be caused by immunologic or non-immunologic mechanisms. Immunologic anaphylaxis can be mediated by IgE-dependent or -independent pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611202/role-of-platelet-derived-tgf%C3%AE-1-in-the-progression-of-ovarian-cancer
#20
Qianghua Hu, Takeshi Hisamatsu, Monika Hammerle, Min Soon Cho, Sunila Pradeep, Rajesha Rupaimoole, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Stephen Tc Wong, Anil K Sood, Vahid Afshar-Kharghan
Transforming growth factor β1 (Tgfß1) plays an important role in cancer.  Most of Tgfß1 in plasma is from platelets, thus we studied whether platelet Tgfß1 has any role in the progression of ovarian cancer, and whether this role is limited to metastasis or also involves the growth of primary tumors. <br /><br />Experimental Design: We compared the growth of murine ovarian cancer cell-induced tumors in platelet-specific Tgfß1 deficient mice and wild-type mice.  Using resected tumor nodules, we studied the effect of platelet Tgfß1 on neoangiogenesis and on platelet extravasation into tumors...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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