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platelet activation,cancer

Beom Jin Lim, Woon-Kyu Lee, Hyun Woong Lee, Kwan Sik Lee, Ja Kyung Kim, Hye Young Chang, Jung Il Lee
BACKGROUND: Platelet-derived growth factor receptor α (PDGFRα) expression is increased in activated hepatic stellate cells (HSCs) in cirrhotic liver, while normal hepatocytes express PDGFRα at a negligible level. However, cancerous hepatocytes may show upregulation of PDGFRα, and hepatocellular carcinoma is preceded by chronic liver injury. The role of PDGFRα in non-cancerous hepatocytes and liver fibrosis is unclear. We hypothesized that upon liver injury, PDGFRα in insulted hepatocytes contributes to liver fibrosis by facilitating intercellular crosstalk between hepatocytes and HSCs...
December 3, 2018: Cell Communication and Signaling: CCS
Giovanni Cimmino, Plinio Cirillo
For many years, the attention on tissue factor (TF) in human pathophysiology has been limited to its role as initiator of extrinsic coagulation pathway. Moreover, it was described as a glycoprotein located in several tissue including vascular wall and atherosclerotic plaque. However, in the last two decades, the discovery that TF circulates in the blood as cell-associated protein, microparticles (MPs) bound and as soluble form, is changing this old vessel-wall TF dogma. Moreover, it has been reported that TF is expressed by different cell types, even T lymphocytes and platelets, and different pathological conditions, such as acute and chronic inflammatory status, and cancer, may enhance its expression and activity...
October 2018: Cardiovascular Diagnosis and Therapy
Liang Shi, Yiming Li, Tingting Yu, Zeng Wang, Chenxi Zhou, Wenxiu Xing, Gaoqi Xu, BingLei Tong, Yingchao Zheng, Jie Zhou, Ping Huang
BACKGROUND Gemcitabine/cisplatin (GP) resistance displays a negative role in treating advanced and metastatic non-small cell lung cancer (NSCLC). Several studies found that the association existed between platelets and cancer antigen 125 (CA125) with anticancer drugs. But the exact correlation between GP resistance and platelet activation index remains poorly understood. MATERIAL AND METHODS Pre-chemotherapy platelet activation index and CA125 were retrospectively evaluated in 169 advanced and metastatic NSCLC patients...
November 30, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yarely M Salinas-Vera, Laurence A Marchat, Dolores Gallardo-Rincón, Erika Ruiz-García, Horacio Astudillo-De La Vega, Raquel Echavarría-Zepeda, César López-Camarillo
Angiogenesis is an important hallmark of cancer serving a key role in tumor growth and metastasis. Therefore, tumor angiogenesis has become an attractive target for development of novel drug therapies. An increased amount of anti‑angiogenic compounds is currently in preclinical and clinical development for personalized therapies. However, resistance to current angiogenesis inhibitors is emerging, indicating that there is a need to identify novel anti‑angiogenic agents. In the last decade, the field of microRNA biology has exploded revealing unsuspected functions in tumor angiogenesis...
November 27, 2018: International Journal of Molecular Medicine
Shaorong Deng, Qing Deng, Yingjie Zhang, Hao Ye, Xiaolan Yu, Yang Zhang, Grace Yq Han, Ping Luo, Mingyuan Wu, Yan Yu, Wei Han
CXCL4 is mainly produced by activated platelets, and certain somatic cells and cancer cells also express CXCL4. However, the physiological function of non-platelet-derived CXCL4 is unclear. Previously, we reported that CXCL4 produced by cancer cells accelerated tumor growth by suppressing the antitumor activities of cytotoxic T lymphocytes (CTLs). To elucidate the mechanism of CXCL4 in tumor immunity, we compared the CTLs and regulatory T cells (Tregs) from CXCL4-/- , CXCR3-/- and C57BL/6 mice overexpressing CXCL4 via intramuscular electroporation...
November 24, 2018: Cancer Letters
Johanna C Bendell, Manish R Patel, Kathleen N Moore, Cynthia C Chua, Hendrik-Tobias Arkenau, Gary Dukart, Kim Harrow, Chris Liang
LESSONS LEARNED: Pharmacokinetic results underscore that the vorolanib (X-82) study design was successful without the need for further dose escalation beyond 400 mg once daily (q.d.).Therefore, the recommended dose of X-82 as a single agent in patients with advanced cancer is 400 mg q.d. BACKGROUND: Vorolanib (X-82) is a novel, oral, multikinase vascular endothelial growth factor (VEGF) receptor/platelet-derived growth factor (PDGF) receptor inhibitor that was developed on the same chemical scaffold as sunitinib, but designed to improve upon the safety profile while maintaining the efficacy of sunitinib...
November 26, 2018: Oncologist
Sandeep Mannava, Kaitlyn E Whitney, Mitchell I Kennedy, Jill King, Grant J Dornan, Katarina Klett, Jorge Chahla, Thos A Evans, Johnny Huard, Robert F LaPrade
PURPOSE: To quantify and compare normative catabolic and anabolic factor concentrations in leukocyte-rich platelet-rich plasma (LR-PRP) at various time points, including baseline, 1 week after initiating naproxen use, and after a 1-week washout period. METHODS: Asymptomatic healthy donors aged between 18 and 70 years were recruited (average age, 36.6 years; range, 25-64 years). Subjects were excluded from the study if they were actively taking any prescribed medications or nonsteroidal anti-inflammatory drugs (NSAIDs) or if they had any of the following at present or previously: blood or immunosuppression disorders, cancer, osteonecrosis, rheumatoid arthritis, avascular necrosis, NSAID intolerance, gastrointestinal or peptic ulcer disease, or kidney dysfunction...
November 21, 2018: Arthroscopy: the Journal of Arthroscopic & related Surgery
Annachiara Mitrugno, Samuel Tassi Tunga, Joanna L Sylman, Jevgenia Zilberman-Rudenko, Toshiaki Shirai, Jessica F Hebert, Robert Kayton, Ying Zhang, Xiaolin Nan, Joseph J Shatzel, Sadik Esener, Matthew T Duvernay, Heidi E Hamm, András Gruber, Craig D Williams, Yumie Takata, Randall Armstrong, Terry K Morgan, Owen J T McCarty
Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. Despite the high incidence of thrombosis in patients with malignancy however, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and TXA2 ...
November 21, 2018: American Journal of Physiology. Cell Physiology
Bibian M E Tullemans, Magdolna Nagy, Siamack Sabrkhany, Arjan W Griffioen, Mirjam G A Oude Egbrink, Maureen Aarts, Johan W M Heemskerk, Marijke J E Kuijpers
Pazopanib is an angiostatic tyrosine kinase inhibitor (TKI) presently used for cancer treatment, particularly in patients with renal cell carcinoma (RCC). This treatment can be accompanied by mild bleeding as an adverse effect. Given the role of protein tyrosine kinases in platelet activation processes, we investigated whether and how pazopanib can affect platelet functions in purified systems and during treatment of advanced RCC patients. In isolated platelets from healthy volunteers, pazopanib dose-dependently reduced collagen-induced integrin activation and secretion, as well as platelet aggregation...
2018: Frontiers in Cardiovascular Medicine
Bo Wang, Rong-Rong Zhou, Shi-Huan Tang
Based on the database of "Dictionary of Traditional Chinese Medicine Prescriptions", high-frequency herbs of Xiaoke disease is mined by traditional Chinese medicine inheritance support system, and core herbs and combinations are discovered through association rules and cluster analysis. On this basis, based on the integrative pharmacology of traditional Chinese medicine to explore the herb-disease relationship, the "herb-compound-target" network is constructed and enriched for the analysis of key target gene functions, metabolic pathways, and their "core herb-target interactions"...
October 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Chan Li, Wei Tian, Feng Zhao, Meng Li, Qin Ye, Yuquan Wei, Tao Li, Ke Xie
Background: Cancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. Thus, we often face a dilemma as to how actively to treat these patients and it would be highly useful to have a simple and powerful indicator of their prognosis...
October 19, 2018: Oncotarget
Qi Luo, Guangyu Wei, Xiaoqing Wu, Kai Tang, Mengdi Xu, Yulu Wu, Yun Liu, Xiaoqian Li, Zengtian Sun, Wen Ju, Kunming Qi, Chong Chen, Zhiling Yan, Hai Cheng, Feng Zhu, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao
BACKGROUND: Platycodin D (PD) is one of the major bioactive components of the roots of Platycodon grandiflorum and possesses multiple biological and pharmacological properties, such as antiviral, anti-inflammatory, and anti-cancer activities. However, whether it affects platelet function remains unclear. This study aims to evaluate the role of PD in platelet function and thrombus formation. METHODS: Platelets were treated with PD followed by measuring platelet aggregation, activation, spreading, clot retraction, expression of glycoprotein receptors...
November 15, 2018: Journal of Translational Medicine
Léa Plantureux, Diane Mège, Lydie Crescence, Françoise Dignat-George, Christophe Dubois, Laurence Panicot-Dubois
Platelets are small anucleate cells that are traditionally described as the major effectors of hemostasis and thrombosis. However, increasing evidence indicates that platelets play several roles in the progression of malignancies and in cancer-associated thrombosis. A notable cross-communication exists between platelets and cancer cells. On one hand, cancer can "educate" platelets, influencing their RNA profiles, the numbers of circulating platelets and their activation states. On the other hand, tumor-educated platelets contain a plethora of active biomolecules, including platelet-specific and circulating ingested biomolecules, that are released upon platelet activation and participate in the progression of malignancy...
November 14, 2018: Cancers
George P Sotiropoulos, Maria Dalamaga, Georgios Antonakos, Ioanna Marinou, Evaggelos Vogiatzakis, Marianna Kotopouli, Irene Karampela, Gerasimos Socrates Christodoulatos, Antigoni Lekka, Athanasios G Papavassiliou
OBJECTIVES: Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS: In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month)...
November 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Keunyoung Kim, Yoon-Kyung Heo, Soyoung Chun, Chang-Hwan Kim, Ok-Nam Bae, Moo-Yeol Lee, Kyung-Min Lim, Jin-Ho Chung
Arsenic-associated carcinogenesis and related mortality are a major public health concern worldwide; however, the underlying mechanism of action remains unclear. Here, we demonstrated that arsenic promotes tumor metastasis by stimulating tumor cell-platelet aggregation (TCPA), which can ultimately increase cancer-related mortality. In freshly isolated human platelets in vitro, arsenic potentiated TCPA prompted by diverse cancer cell lines, which was attributable to increased platelet reactivity to TCPA with respect to thrombin generation and P-selectin, GPIIb/IIIa expression...
November 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Orazio Fortunato, Cristina Borzi, Massimo Milione, Giovanni Centonze, Davide Conte, Mattia Boeri, Carla Verri, Massimo Moro, Federica Facchinetti, Francesca Andriani, Luca Roz, Laura Caleca, Veronica Huber, Agata Cova, Chiara Camisaschi, Chiara Castelli, Valeria Cancila, Claudio Tripodo, Ugo Pastorino, Gabriella Sozzi
miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell-type specific expression pattern and topography of several miRNAs such as mir-145 in fibroblasts, mir-126 in endothelial cells, mir-133a in skeletal muscle cells was observed in normal and lung cancer tissues...
November 13, 2018: International Journal of Cancer. Journal International du Cancer
Javier Sánchez Ramírez, Mónica Bequet-Romero, Yanelys Morera Díaz, Francisco Hernández-Bernal, Ana de la Torre Santos, Katty-Hind Selman-Housein Bernal, Yenima Martín Bauta, Cimara H Bermúdez Badell, Miladys Limonta Fernández, Marta Ayala Avila
Two phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as "Platelet VEGF". This methodology is based on the estimation of VEGF within platelets by subtracting the plasma VEGF level from the serum level and dividing this by the platelet count, and then this latter expression is additionally corrected by the hematocrit...
November 2018: Heliyon
Oscar J Cordero, Rubén Varela-Calviño
Many evidences support that species from the Human Oral Microbiome Database such as Fusobacterium nucleatum or Bacteroides, linked previously to periodontitis and appendicitis, play a role in colorectal cancer (CRC), including metastasis. These typically oral species are invasive anaerobes that form biofilms in their virulent state. Aspirin (a NSAID) has been recently included into routine CRC prevention rationale. NSAIDs can prevent the growth of neoplastic lesions by inhibiting COX enzymes and another set of recently identified COX-independent targets, which include the WNT, AMPK and MTOR signaling pathways, the crosstalk between nucleoli and NF-κB transcriptional activity in apoptosis, and the biochemistry of platelets...
October 2018: Heliyon
C Arnold Spek, Cansu Tekin, Maarten F Bijlsma
Protease activated receptor 1 (PAR-1), originally identified as the thrombin receptor on platelets and vascular endothelial cells, is expressed on numerous cells throughout the body. Tumor cells, and cells in the tumor microenvironment like cancer-associated fibroblasts, macrophages, T cells and endothelial cells, are no exception and PAR-1 expression is abundant in a variety of cancer tissues [1,2]. The potential relevance of PAR-1 expression for tumor growth is underscored by observations that PAR-1 expression levels correlate with cancer progression and overall survival [1,2]...
November 9, 2018: Journal of Thrombosis and Haemostasis: JTH
Rieko Oyama, Fusako Kito, Zhiwei Qiao, Marimu Sakumoto, Kumiko Shiozawa, Shunichi Toki, Akihiko Yoshida, Akira Kawai, Tadashi Kondo
Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor β (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research. Here, we established novel patient-derived DFSP cell lines from two patients with DFSP and designated these cell lines NCC-DFSP1-C1 and NCC-DFSP2-C1...
November 8, 2018: In Vitro Cellular & Developmental Biology. Animal
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