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Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2742-2756页

作者： Li-Jun Zhao Zhi-Yin Wang Wei-Ting Liu Li-Li Yu Hao-Nan Qi Jie Ren Chen-Guang Zhang Hematology Laboratory The First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453100Henan ProvinceChina Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy School of Medical TechnologyXinxiang Medical UniversityXinxiang 453003Henan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiang 453003Henan ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

关键词： platelets Antiplatelet therapy Hepatocellular carcinoma Aspirin Antitumor

Emerging applications of tumour-educated platelets in the detection and prognostication of ovarian cancer

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蛋白质与细胞:英文版 2023年第8期14卷 556-559页

作者： Jiewei Zhu Vasily Giannakeas Steven A.Narod Mohammad R.Akbari Women's College Research Institute Women's College HospitalUniversity of TorontoTorontoOntario M5S 1B2Canada Department of Medicine University of TorontoTorontoOntario MSS 1ACanada Institute of Medical Science Faculty of MedicineUniversity of TorontoTorontoOntario MSS 1ACanada Dalla Lana School of Public Health University of TorontoTorontoOntario MSS 1ACanada

platelets are nuclear cell fragments produced by megakaryocytes.Inactive platelets circulate in the blood until activation by extemal stimuli to execute important biological functions,including hemostasis,inflammation,tissue remodelling,and blood vessel formation.platelets can reflect cancer cells'pathogenesis through a process known as tumour-educated platelets(TEPs).

关键词： Platelet tumour platelets

Inflammation: Complexity and significance of cellular and molecular responses

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Journal of Acute Disease 2024年第1期13卷 3-7页

作者： Serdar Ozdemir University of Health Science Umraniye Training and Research HospitalIstanbulTurkey

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

关键词： Inflammation C-reactive protein platelets SCUBE1 Adrenomedullin Calprotectin Pentraxin-3 Immune response Acute phase response Vascular function

Effects of platelets on characteristics of lymphocytes cultured in vitro and optimization of adoptive immunotherapy

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BIOCELL 2023年第12期47卷 2661-2669页

作者： CONGLIANG CHEN XIAOHONG LENG YU ZHANG JUNMEI HU DAPENG WEI PEIPEI WANG XIA WANG West China School of Basic Medical Sciences and Forensic Medicine Department of ImmunologySichuan UniversityChengduChina

T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regulation and immune killing.Studies have shown that platelets play a crucial role in maintaining the stable differentiation of lymphocytes and the balance in immunomodulation.Therefore,it is necessary to study the effect of platelets on lymphocytes in vitro to better understand the role of platelets in the immune system and broaden the application of adoptive immunotherapy.Methods:Cell counting and microscopic observation were used to detect the effect of activated platelets on lymphocyte proliferation in vitro;Flow cytometry was used to detect whether changes in platelet activity affect the proportion of lymphocyte subpopulations in vitro,and to detect differences in the expression of granzyme B;lactate dehydrogenase assay(LDH)was used to determine the difference in lymphocyte killing activity caused by platelet activity in vitro.Results:This was the first to promote lymphocyte proliferation through the expression or release of certain molecules in vitro,demonstrating that platelet activation is one of the key factors.Secondly,activated platelets or inactivated platelets promoted lymphocyte subset differentiation by enhancing the proportion of CD3+CD8+T lymphocytes(CTL cells)but had a slight effect on the proportion of CD3+CD4+T(Th cells)and CD4+CD25+T lymphocytes(Treg cells).Then,it was found that either activated platelets or inactivated platelets down-regulated the proportion of natural killer(NK)T lymphocytes,while activated platelets significantly enhance the proportion of NK lymphocytes.Therefore,by further detecting the killing activity of PBMCs treated with platelets,it was found that activated platelets promoted the extensive anti-tumor activity of lymphocytes and significantly increased the expression of granzyme B.Conclusion:Our results suggest that activated platelets promote lymphocyte prol

关键词： platelets Lymphocyte Adoptive immunotherapy

platelets in hemostasis and thrombosis:Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis

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The Journal of Biomedical Research 2015年第6期29卷 437-444页

作者： Yan Hou Naadiya Carrim Yiming Wang Reid C.Gallant Alexandra Marshall Heyu Ni Department of Laboratory Medicine Keenan Research Centre for Biomedical ScienceLi Ka Shing Knowledge InstituteSt.Michael's Hospital and Toronto Platelet Immunobiology Group Jilin Provincial Center for Disease Control and Prevention Department of Laboratory Medicine and Pathobiology University of Toronto Canadian Blood Services Department of Medicine and Department of Physiology University of Toronto

platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.

关键词： platelets thrombosis and hemostasis integrin αIIbβ3 fibrinogen fibronectin

platelets in Kawasaki disease:Is this only a numbers game or something beyond?

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Genes & Diseases 2020年第1期7卷 62-66页

作者： Kanika Arora Sandesh Guleria Ankur Kumar Jindal Amit Rawat Surjit Singh Allergy Immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery abnormalities.KD is now the most common cause of acquired heart disease in developed countries.Thrombocytosis is consistently found in patients with KD,usually in 2nd to 3rd week of illness.Thrombocytopenia has occasionally been reported in the acute phase of KD.An increase or decrease in platelet number in patients with KD was initially considered to be a benign phenomenon.However,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather activated.This phenomenon has been found to increase the risk of thrombosis in these patients.Similarly a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of disease.In this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.

关键词： Aspirin CD40 ligand Kawasaki disease Platelet derived microparticles platelets Thrombosis

platelets Play an Integral Role in Body Heat Production and Maintenance: A Newly Proposed Function

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Journal of Biosciences and Medicines 2023年第3期11卷 37-47页

作者： Thirugnana Subramanian Department of Pediatric Hematology and Oncology Washington University School of Medicine Saint Louis MO USA

In platelets, most of the ADP is stored in dense granules and released into extracellular space through exocytosis as a signaling molecule upon platelet activation. Glycolysis and the TCA cycle consume considerable amounts of ADP;however, limiting quantities of available ADP to make ATP through OXPHOS result in failure of ATP production and release of energy as heat into the surroundings. Thus, body heat may be a potential product of circulating platelets. Furthermore, the incomplete OXPHOS process causes the production of ROS that leads to earlier platelet death resulting in shorter life span. In the future, this new function may have a wide variety of clinical applications.

关键词： ADP ATP Oxidative Phosphorylation platelets Reactive Oxygen Species

platelets in ischemic heart disease: friends or foes?

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中国药理学与毒理学杂志 1998年第1期12卷 4-12页

作者：ＪａｗａｈａｒＬＭＥＨＴＡＹＡＮＧＢａｉ-Ｃｈｕｎ Department of Medicine University of Florida Gainesville FL 32610 United States

Ｐｌａｔｅｌｅｔｓｉｎｉｓｃｈｅｍｉｃｈｅａｒｔｄｉｓｅａｓｅ：ｆｒｉｅｎｄｓｏｒｆｏｅｓ？１ＪａｗａｈａｒＬＭＥＨＴＡ，ＹＡＮＧＢａｉ－Ｃｈｕｎ（ＤｅｐａｒｔｍｅｎｔｏｆＭｅｄｉｃｉｎｅ，ＵｎｉｖｅｒｓｉｔｙｏｆＦ... 详细信息

Ｐｌａｔｅｌｅｔｓｉｎｉｓｃｈｅｍｉｃｈｅａｒｔｄｉｓｅａｓｅ：ｆｒｉｅｎｄｓｏｒｆｏｅｓ？１ＪａｗａｈａｒＬＭＥＨＴＡ，ＹＡＮＧＢａｉ－Ｃｈｕｎ（ＤｅｐａｒｔｍｅｎｔｏｆＭｅｄｉｃｉｎｅ，ＵｎｉｖｅｒｓｉｔｙｏｆＦｌｏｒｉｄａ，Ｇａｉｎｅｓｖｉｌｅ...

关键词： platelets reperfusioninjury

Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor

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World Journal of Gastroenterology 2019年第41期25卷 6248-6257页

作者： Shuai-Shuai Xu Hua-Xiang Xu Wen-Quan Wang Shuo Li Hao Li Tian-Jiao Li Wu-Hu Zhang Liang Liu Xian-Jun Yu Department of Pancreatic Surgery Fudan University Shanghai Cancer CenterShanghai 20032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Shanghai Pancreatic Cancer Institute Shanghai 200032China Pancreatic Cancer Institute Fudan UniversityShanghai 200032China

BACKGROUND platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocrine tumor(pNET)lacks adequate literature support.The predictive value of tumor-infiltrating platelets(TIPs)in pNET remains unclear.AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection.METHODS In total,113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study.Immunohistochemical analysis of cluster of differentiation 42b(CD42b)expression in the tumor specimens was performed to determine the presence of TIPs.Univariate and multivariate analyses were used to analyze the prognostic value of TIPs.RESULTS TIPs were observed in intratumoral areas in 54 patients.Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs(all P>0.05).Patients with positive intratumoral CD42b expression had worse overall survival(P=0.005)and recurrence-free survival(P0.05).CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET,and their detection represents a promising tool for pNET treatment strategy decisions.

关键词： Tumor-infiltrating platelets Pancreatic neuroendocrine tumor Survival Recurrence Platelet count Mean platelet volume Platelet-to-lymphocyte ratio