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Chen Z, Xu L, Yuan Y, Zhang S, Xue R. Metabolic crosstalk between platelets and cancer: Mechanisms, functions, and therapeutic potential. Semin Cancer Biol 2025; 110:65-82. [PMID: 39954752 DOI: 10.1016/j.semcancer.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/30/2025] [Accepted: 02/03/2025] [Indexed: 02/17/2025]
Abstract
Platelets, traditionally regarded as passive mediators of hemostasis, are now recognized as pivotal regulators in the tumor microenvironment, establishing metabolic feedback loops with tumor and immune cells. Tumor-derived signals trigger platelet activation, which induces rapid metabolic reprogramming, particularly glycolysis, to support activation-dependent functions such as granule secretion, morphological changes, and aggregation. Beyond self-regulation, platelets influence the metabolic processes of adjacent cells. Through direct mitochondrial transfer, platelets reprogram tumor and immune cells, promoting oxidative phosphorylation. Additionally, platelet-derived cytokines, granules, and extracellular vesicles drive metabolic alterations in immune cells, fostering suppressive phenotypes that facilitate tumor progression. This review examines three critical aspects: (1) the distinctive metabolic features of platelets, particularly under tumor-induced activation; (2) the metabolic crosstalk between activated platelets and other cellular components; and (3) the therapeutic potential of targeting platelet metabolism to disrupt tumor-promoting networks. By elucidating platelet metabolism, this review highlights its essential role in tumor biology and its therapeutic implications.
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Affiliation(s)
- Zhixue Chen
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lin Xu
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yejv Yuan
- The First Affiliated Hospital of Anhui University of Science and Technology, Huainan 232001, China
| | - Si Zhang
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
| | - Ruyi Xue
- Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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Reghukumar SK, Inkielewicz-Stepniak I. Tumour cell-induced platelet aggregation in breast cancer: Scope of metal nanoparticles. Biochim Biophys Acta Rev Cancer 2025; 1880:189276. [PMID: 39921012 DOI: 10.1016/j.bbcan.2025.189276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 01/30/2025] [Accepted: 02/01/2025] [Indexed: 02/10/2025]
Abstract
Breast cancer is a major cause of cancer-related mortality among the female population worldwide. Among the various factors promoting breast cancer metastasis, the role of cancer-cell platelet interactions leading to tumour cell-induced platelet aggregation (TCIPA) has garnered significant attention recently. Our state-of-the-art literature review verifies the implications of metal nanoparticles in breast cancer research and TCIPA-specific breast cancer metastasis. We have evaluated in vitro and in vivo research data as well as clinical investigations within the scope of this topic presented in the last ten years. Nanoparticle-based drug delivery platforms in cancer therapy can combat the growing concerns of multi-drug resistance, the alarming rates of chemotherapy-induced toxicities and cancer progression. Metal nanoparticles conjugated with chemotherapeutics can outperform their free drug counterparts in achieving targeted drug delivery and desired drug concentration inside the tumour tissue with minimal toxic effects. Existing data highlights the potential of metal nanoparticles as a promising tool for targeting the platelet-specific interactions associated with breast cancer metastasis including TCIPA.
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Ji W, Xiong Y, Yang W, Shao Z, Guo X, Jin G, Su J, Zhou M. Transcriptomic profiling of blood platelets identifies a diagnostic signature for pancreatic cancer. Br J Cancer 2025:10.1038/s41416-025-02980-z. [PMID: 40133510 DOI: 10.1038/s41416-025-02980-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 02/26/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Pancreatic cancer (PaCa) is a deadly malignancy that is often diagnosed at an advanced stage, limiting treatment and reducing survival. There is an urgent need for convenient and accurate diagnostic markers for the early detection of PaCa. METHODS In this multicenter case-control study, we performed transcriptome analysis of 673 platelet samples from different in-house and public cohorts. RNA sequencing and RT-qPCR were used to discover and validate potential platelet biomarkers. A multi-gene signature was developed using binomial generalized linear model and independently validated in multicenter cohorts. RESULTS Two platelet RNAs, SCN1B and MAGOHB, consistently showed robust altered expression patterns between PaCa and healthy controls across cohorts, as confirmed by both RNA sequencing and RT-qPCR. The diagnostic two-RNA signature, PLA2Sig, demonstrated remarkable performance in detecting PaCa, with area under the receiver operating characteristic curve (AUC) values of 0.808, 0.900, 0.783, and 0.830 across multicenter cohorts. Furthermore, PLA2Sig effectively identified resectable stage I&II PaCa cases with an AUC of 0.812. Notably, PLA2Sig outperformed the traditional serum markers carcinoembryonic antigen and carbohydrate antigen 19-9 in distinguishing PaCa from healthy controls, and is complementary to established blood-based screening biomarkers. CONCLUSION These findings provide preliminary but promising evidence for the potential utility of platelet RNAs as an alternative non-invasive liquid biopsy tool for the early detection of PaCa.
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Affiliation(s)
- Weiping Ji
- Department of General Surgery, School of Biomedical Engineering, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Yichun Xiong
- Department of General Surgery, School of Biomedical Engineering, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Wei Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, China
| | - Zhuo Shao
- Department of General Surgery, Shanghai Changhai Hospital of Navy Medical University, Shanghai, 200438, China
| | - Xiaoling Guo
- Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Gang Jin
- Department of General Surgery, Shanghai Changhai Hospital of Navy Medical University, Shanghai, 200438, China
| | - Jianzhong Su
- Department of General Surgery, School of Biomedical Engineering, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
| | - Meng Zhou
- Department of General Surgery, School of Biomedical Engineering, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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Miao L, Yang Y, Cheng M, Chen L, Han C. Ginsenoside Rb prevents the metastasis of hepatocarcinoma by blocking the platelet-tumor cell interaction. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1721-1733. [PMID: 39172150 DOI: 10.1007/s00210-024-03387-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 08/15/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND The interaction between platelets and tumor cells is a crucial step in the progression of tumor metastasis. Blocking platelet-tumor cell interaction is a potential target against metastasis. Ginsenoside Rb (G-Rb) exhibits potential anti-tumor pharmacological properties and may offer a therapeutic option for cancer. PURPOSE This study aimed to investigate anti-metastatic effects of G-Rb through regulating the crosstalk of platelets with tumor cells. METHODS In order to explore anti-metastatic effects of G-Rb in vitro, HepG2 cell and platelets were co-cultured to mimic the interaction of platelets with tumor cells. Wound healing and Transwell assays were used to assess the effect of G-Rb on cell migration and invasion. The expression of epithelial-mesenchymal transition (EMT)-related markers was determined by RT-qPCR and western blot assays. The aggregation and activation of platelets were detected by flow cytometry. Moreover, a lung metastasis model of mice was established to evaluate inhibitory effects of G-Rb in vivo. Metastatic nodules on the lung surface were counted and sections of lung tissues were stained by H&E. RESULTS G-Rb effectively suppressed tumor metastasis in the co-culture of platelets with HepG2 cell. First, G-Rb treatment significantly inhibited the migration and invasion of HepG2 cells induced by platelets. Second, the expressions of EMT-related markers, including N-cadherin, Snail, and MMP9, were decreased by the treatment of G-Rb in the presence of platelets. Meanwhile, G-Rb also suppressed platelet hyperactivity by regulating the adhesion to tumor cells, activation, TCIPA, and TGF-β1 secretion of platelets in vitro. In addition, the results of in vivo experiments proved G-Rb administration not only significantly decreased lung metastasis but also attenuated platelets aberrant aggregation and activation in vivo. CONCLUSION Our findings showed that G-Rb inhibited tumor metastasis and platelet activation through mediating platelet-tumor cell interaction, indicating the potential values of G-Rb in tumor metastasis therapy.
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Affiliation(s)
- Longxing Miao
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China
- The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People's Republic of China
| | - Yijun Yang
- Department of Pharmacy, Shandong Medical College, Jinan, 250002, People's Republic of China
| | - Mengtao Cheng
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China
| | - Lijing Chen
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China
- The Second Affiliated Hospital of Shandong, University of Traditional Chinese Medicine, Jinan, 250000, People's Republic of China
| | - Chunchao Han
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People's Republic of China.
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Demir B, Abuzaid G. Association Between Mean Platelet Volume, Platelet Count, and Distribution Width With Depth of Invasion in Oral Cancers. EAR, NOSE & THROAT JOURNAL 2025; 104:NP40-NP45. [PMID: 35411813 DOI: 10.1177/01455613211032532] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION To examine the potential predictive roles of the preoperative mean platelet volume (MPV), platelet count (PC), and platelet distribution width (PDW) in patients with oral cancer and their association with the depth of invasion (DOI). METHODS This retrospective study included 122 patients (66 males, 56 females) diagnosed with oral cancer between January 2009 and January 2015 by our Otolaryngology Department. At diagnosis, the mean age was 64.6 ± 13.9 years. The average follow-up period was 39.2 ± 23.9 months. RESULTS We found significant differences in all parameters (PDW, MPV, PC) based on the positivity of the lymph node and the tumor stage. The mean PDW, MPV, and PC were significantly higher in the exitus group than in the survivor group (P = .010, .036, and .047, respectively). In patients with high PDW, we observed a lower progression-free survival. We observed that PDW had a significant impact on the recurrence of the disease. Platelet distribution width, MPV, and PC were significant prognostic factors. A high PDW increased fatality 4.1 times, and a high MPV increased fatality 4.7 times (P = .040 and .032, respectively). We found in a univariate analysis that tumor grade, PDW, MPV, and PC were predictive factors for fatality. On multivariate analysis, we found that MPV, PC, and predictors were independent of tumor grade. We observed an association between MPV and DOI. CONCLUSION High PC, MPV, and PDW could be meaningful prognostic predictors for low survival rates. Mean platelet volume appears to be a more effective marker because it is associated with the DOI and prognosis. However, further research is required to confirm our findings.
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Affiliation(s)
- Berat Demir
- Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Medical Faculty, Pendik Training and Research Hospital, Istanbul, Turkey
| | - Ghazi Abuzaid
- Department of Otorhinolaryngology-Head and Neck Surgery, Marmara University Medical Faculty, Pendik Training and Research Hospital, Istanbul, Turkey
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Faria PCL, Resende RS, Cardoso AM. Metastasis and angiogenesis in cervical cancer: key aspects of purinergic signaling in platelets and possible therapeutic targets. Purinergic Signal 2024; 20:607-616. [PMID: 38753131 PMCID: PMC11554953 DOI: 10.1007/s11302-024-10020-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 05/09/2024] [Indexed: 11/13/2024] Open
Abstract
Cervical cancer ranks as the fourth most common and fatal cancer among women worldwide. Studies have demonstrated a strong association between purinergic platelet signaling and tumor progression in this type of cancer. The literature shows that neoplastic cells, when in the bloodstream, secrete adenosine triphosphate (ATP) and adenosine nucleotide diphosphate (ADP) that act on their corresponding platelet P2Y and P2X receptors. The interaction of these nucleotides with their receptors results in platelet activation and degranulation, ensuing several consequences, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor, matrix metalloproteinases, ADP, and ATP. These molecules play essential roles in angiogenesis and tumor metastasis in cervical cancer. Several purinergic receptors are found in endothelial cells. Their activation, especially P2Y2, by the nucleotides released by platelets can induce relaxation of the endothelial barrier and consequent extravasation of tumor cells, promoting the development of metastases. Cancer cells that enter the bloodstream during the metastatic process are also subject to high shear stress and immune surveillance. In this context, activated platelets bind to circulating tumor cells and protect them against shear stress and the host's immune system, especially against natural killer cells, facilitating their spread throughout the body. Furthermore, activation of the P2Y12 receptor present on the platelet surface promotes the release of VEGF, the main inducer of angiogenesis in cervical cancer, in addition to increasing the concentration of several other pro-angiogenic molecules. Therefore, this review will address the role of platelet purinergic signaling in tumor progression of cervical cancer and propose possible therapeutic targets.
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Affiliation(s)
- Paula C L Faria
- Medical School, Federal University of Fronteira Sul, Chapecó, SC, Brazil
| | - Rackel S Resende
- Medical School, Federal University of Fronteira Sul, Chapecó, SC, Brazil
| | - Andréia M Cardoso
- Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
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Chen J, Liu S, Ruan Z, Wang K, Xi X, Mao J. Thrombotic events associated with immune checkpoint inhibitors and novel antithrombotic strategies to mitigate bleeding risk. Blood Rev 2024; 67:101220. [PMID: 38876840 DOI: 10.1016/j.blre.2024.101220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/23/2024] [Accepted: 06/05/2024] [Indexed: 06/16/2024]
Abstract
Although immunotherapy is expanding treatment options for cancer patients, the prognosis of advanced cancer remains poor, and these patients must contend with both cancers and cancer-related thrombotic events. In particular, immune checkpoint inhibitors are associated with an increased risk of atherosclerotic thrombotic events. Given the fundamental role of platelets in atherothrombosis, co-administration of antiplatelet agents is always indicated. Platelets are also involved in all steps of cancer progression. Classical antithrombotic drugs can cause inevitable hemorrhagic side effects due to blocking integrin β3 bidirectional signaling, which regulates simultaneously thrombosis and hemostasis. Meanwhile, many promising new targets are emerging with minimal bleeding risk and desirable anti-tumor effects. This review will focus on the issue of thrombosis during immune checkpoint inhibitor treatment and the role of platelet activation in cancer progression as well as explore the mechanisms by which novel antiplatelet therapies may exert both antithrombotic and antitumor effects without excessive bleeding risk.
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Affiliation(s)
- Jiayi Chen
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Shuang Liu
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zheng Ruan
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Kankan Wang
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Xiaodong Xi
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Jianhua Mao
- Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
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Zhao J, Zhang K, Sui D, Wang S, Li Y, Tang X, Liu X, Song Y, Deng Y. Recent advances in sialic acid-based active targeting chemoimmunotherapy promoting tumor shedding: a systematic review. NANOSCALE 2024; 16:14621-14639. [PMID: 39023195 DOI: 10.1039/d4nr01740d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.
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Affiliation(s)
- Jingyi Zhao
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Kunfeng Zhang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Dezhi Sui
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Shuo Wang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yantong Li
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Xueying Tang
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Xinrong Liu
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yanzhi Song
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
| | - Yihui Deng
- College of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
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Tuerhong N, Yang Y, Wang C, Huang P, Li Q. Interactions between platelets and the cancer immune microenvironment. Crit Rev Oncol Hematol 2024; 199:104380. [PMID: 38718939 DOI: 10.1016/j.critrevonc.2024.104380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 04/30/2024] [Accepted: 05/02/2024] [Indexed: 06/16/2024] Open
Abstract
Cancer is a leading cause of death in both China and developed countries due to its high incidence and low cure rate. Immune function is closely linked to the development and progression of tumors. Platelets, which are primarily known for their role in hemostasis, also play a crucial part in the spread and progression of tumors through their interaction with the immune microenvironment. The impact of platelets on tumor growth and metastasis depends on the type of cancer and treatment method used. This article provides an overview of the relationship between platelets and the immune microenvironment, highlighting how platelets can either protect or harm the immune response and cancer immune escape. We also explore the potential of available platelet-targeting strategies for tumor immunotherapy, as well as the promise of new platelet-targeted tumor therapy methods through further research.
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Affiliation(s)
- Nuerye Tuerhong
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China; West China Biomedical Big Data Center, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China
| | - Yang Yang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China; West China Biomedical Big Data Center, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China
| | - Chenyu Wang
- The Second Clinical Medical College, Lanzhou university, No. 222 South Tianshui Road, Gansu, China
| | - Peng Huang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China; West China Biomedical Big Data Center, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China
| | - Qiu Li
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China; West China Biomedical Big Data Center, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China.
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Sun L, Yang L, Du X, Liu L, Ran Q, Yang Q, Chen Y, Zhu X, Li Q. Ethyl-acetate extract of Spatholobi Caulis blocked the pro-metastatic support from the hemato-microenvironment of colon cancer by specific disruption of tumor-platelet adhesion. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155420. [PMID: 38547619 DOI: 10.1016/j.phymed.2024.155420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 02/01/2024] [Accepted: 02/03/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Within the pro-metastatic hemato-microenvironment, interaction between platelets and tumor cells provides essential support for tumor cells by inducing Epithelial-Mesenchymal Transition (EMT), which greatly increases the stemness of colon cancer cells. Pharmacologically, although platelet deactivation has proved to be benefit against metastasis, its wide application is severely restricted due to the bleeding risk. Spatholobi Caulis, a traditional Chinese herb with circulatory promotion and blood stasis removal activity, has been proved to be clinically effective in malignant medication, leaving its mechanistic relevance to tumor-platelet interaction largely unknown. METHODS Firstly, MC38-Luc cells were injected into tail-vein in C57BL/6 mice to establish hematogenous metastasis model and the anti-metastasis effects of SEA were evaluated by using a small-animal imaging system. Then, we evaluated the anti-tumor-platelet interaction efficacy of SEA using a tumor-specific induced platelet aggregation model. Platelet aggregation was specifically induced by tumor cells in vitro. Furthermore, to clarify the anti-metastatic effects of SEA is mainly attributed to its blockage on tumor-platelet interaction, after co-culture with tumor cells and platelets (with or without SEA), MC38-Luc cells were injected into the tail-vein and finally count the total of photons quantitatively. Besides, to clarify the blocking pattern of SEA within the tumor-platelet complex, the dependence of SEA on different fractions from activated platelets was tested. Lastly, molecular docking screening were performed to screen potential effective compounds and we used β-catenin blockers to verify the pathways involved in SEA blocking tumor-platelet interaction. RESULTS Our study showed that SEA was effective in blocking tumor-platelet specific interaction: (1) Through CCK-8 and LDH assays, SEA showed no cytotoxic effects on tumor cells and platelets. On this basis, by the tail vein injection model, the photon counts in the SEA group was significantly lower than model group, indicating that SEA effectively reduced metastasis. (2) In the "tumor-platelet" co-culture model, SEA effectively inhibited the progression of EMT and cancer stemness signatures of MC38 cells in the model group. (3) In mechanism study, by using the specific inhibitors for galectin-3 (GB1107) andWNT (IWR) respectively, we proved that SEA inhibits the activation of the galectin-3-mediated β-catenin activation. CONCLUSION By highlighting the pro-metastatic effects of galectin-3-mediated tumor-platelet adhesion, our study provided indicative evidence for Spatholobi Caulis as the representative candidate for anti-metastatic therapy.
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Affiliation(s)
- Lidong Sun
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - Lina Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - Xinke Du
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - Li Liu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - QingSen Ran
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - Qing Yang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - Ying Chen
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China
| | - XiaoXin Zhu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China.
| | - Qi Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, State key laboratory for quality ensurance and sustainable use of Dao-di herbs, Beijing 100700, China.
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Yu L, Wang L, Xue Y, Ren Y, Liu T, Hu H. Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1400573. [PMID: 38841303 PMCID: PMC11151168 DOI: 10.3389/fendo.2024.1400573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 04/22/2024] [Indexed: 06/07/2024] Open
Abstract
Background and aims Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study. Methods Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer's disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses. Results Multivariable MR analysis showed causal association between Alzheimer's disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer's disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer's disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer's disease, and LIHC susceptibility. Conclusions A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer's disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.
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Affiliation(s)
- Lihua Yu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
| | - Leisheng Wang
- Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yilin Ren
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Tianhao Liu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Hao Hu
- Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
- Wuxi Institute of Hepatobiliary Surgery, Wuxi, China
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12
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Heo JH, Yun J, Kim KH, Jung JW, Yoo J, Kim YD, Nam HS. Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies. J Stroke 2024; 26:164-178. [PMID: 38836266 PMCID: PMC11164583 DOI: 10.5853/jos.2023.03279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/29/2024] [Accepted: 01/29/2024] [Indexed: 06/06/2024] Open
Abstract
Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.
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Affiliation(s)
- Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
- Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, Korea
| | - Jaeseob Yun
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Hyun Kim
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Wook Jung
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Joonsang Yoo
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Young Dae Kim
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
- Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, Korea
| | - Hyo Suk Nam
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
- Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Seoul, Korea
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Aleksandrowicz K, Hempel D, Polityńska B, Wojtukiewicz AM, Honn KV, Tang DG, Wojtukiewicz MZ. The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System. Semin Thromb Hemost 2024; 50:462-473. [PMID: 37984359 DOI: 10.1055/s-0043-1776875] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin, initiates platelet activation, and promotes clot formation. Thrombin also activates anticoagulant pathways, indirectly inhibiting factors involved in coagulation. Tissue factor triggers thrombin generation, and the overexpression of thrombin in various cancers suggests that it is involved in tumor growth, angiogenesis, and metastasis. Increased thrombin generation has been observed in cancer patients, especially those with metastases. Thrombin exerts its effects through protease-activated receptors (PARs), particularly PAR-1 and PAR-2, which are involved in cancer progression, angiogenesis, and immunological responses. Thrombin-mediated signaling promotes angiogenesis by activating endothelial cells and platelets, thereby releasing proangiogenic factors. These functions of thrombin are well recognized and have been widely described. However, in recent years, intriguing new findings concerning the association between thrombin activity and cancer development have come to light, which justifies a review of this research. In particular, there is evidence that thrombin-mediated events interact with the immune system, and may regulate its response to tumor growth. It is also worth reevaluating the impact of thrombin on thrombocytes in conjunction with its multifaceted influence on tumor progression. Understanding the role of thrombin/PAR-mediated signaling in cancer and immunological responses is crucial, particularly in the context of developing immunotherapies. In this systematic review, we focus on the impact of the thrombin-related immune system response on cancer progression.
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Affiliation(s)
- Karolina Aleksandrowicz
- Department of Clinical Oncology, Medical University, Białystok, Poland
- Comprehensive Cancer Center, Bialystok, Poland
| | - Dominika Hempel
- Department of Clinical Oncology, Medical University, Białystok, Poland
- Comprehensive Cancer Center, Bialystok, Poland
| | - Barbara Polityńska
- Department of Psychology and Philosophy, Medical University of Białystok, Białystok, Poland
| | - Anna M Wojtukiewicz
- Department of Psychology and Philosophy, Medical University of Białystok, Białystok, Poland
| | - Kenneth V Honn
- Department of Pathology-School of Medicine, Bioactive Lipids Research Program, Detroit, Michigan
- Department of Chemistry, Wayne State University, Detroit, Michigan
- Department of Oncology, Wayne State University, Detroit, Michigan
| | - Dean G Tang
- Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Marek Z Wojtukiewicz
- Department of Clinical Oncology, Medical University, Białystok, Poland
- Comprehensive Cancer Center, Bialystok, Poland
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14
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Wang Y, Dong A, Jin M, Li S, Duan Y. TEP RNA: a new frontier for early diagnosis of NSCLC. J Cancer Res Clin Oncol 2024; 150:97. [PMID: 38372784 PMCID: PMC10876732 DOI: 10.1007/s00432-024-05620-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 01/10/2024] [Indexed: 02/20/2024]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers. PURPOSE Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article. CONCLUSION The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.
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Affiliation(s)
- Yuan Wang
- Clinical Laboratory, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang Medical University, Weifang, 261000, Shandong, China
- Department of Clinical Laboratory Science, Weifang Medical University, Weifang, 261000, Shandong, China
| | - Aiping Dong
- Clinical Laboratory, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang Medical University, Weifang, 261000, Shandong, China
| | - Minhan Jin
- Clinical Laboratory, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang Medical University, Weifang, 261000, Shandong, China
- Department of Clinical Laboratory Science, Weifang Medical University, Weifang, 261000, Shandong, China
| | - Shirong Li
- Clinical Laboratory, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang Medical University, Weifang, 261000, Shandong, China.
| | - Yang Duan
- Clinical Laboratory, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang Medical University, Weifang, 261000, Shandong, China.
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15
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Xie J, Guo Z, Zhu Y, Ma M, Jia G. Peripheral blood inflammatory indexes in breast cancer: A review. Medicine (Baltimore) 2023; 102:e36315. [PMID: 38050296 PMCID: PMC10695498 DOI: 10.1097/md.0000000000036315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 11/03/2023] [Indexed: 12/06/2023] Open
Abstract
Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the changes in inflammatory cells may affect the occurrence and development of tumors. Complete blood count at the time of diagnosis and treatment can reflect the inflammatory status within the tumor. Studies have shown that the number of certain inflammatory cells in peripheral blood and their ratios are important prognostic factors for many malignancies, including neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index and pan-immune-inflammation-value. The value of peripheral blood inflammation indexes in predicting the efficacy and prognosis of breast cancer neoadjuvant therapy is worth recognizing. This review details the application of peripheral blood inflammation indexes in the evaluation of efficacy and prediction of prognosis in neoadjuvant therapy for breast cancer, aiming to provide a more comprehensive reference for the comprehensive diagnosis and treatment of breast cancer.
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Affiliation(s)
- Jiaqiang Xie
- Department of Breast and Thyroid Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
- School of Clinical Medicine, Henan University, Kaifeng, Henan, China
| | - Zhenxi Guo
- Department of Breast and Thyroid Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
- School of Clinical Medicine, Henan University, Kaifeng, Henan, China
| | - Yijing Zhu
- Department of Breast and Thyroid Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
- School of Clinical Medicine, Henan University, Kaifeng, Henan, China
| | - Mingde Ma
- Department of Breast and Thyroid Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
| | - Guangwei Jia
- Department of Thyroid and Breast Surgery, Nanyang First People’s Hospital Affiliated to Henan University, Nanyang, Henan, China
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Li M, Gui J, Wang H, An J, Wu R, Liu X, Wu B, Xiao H. Prognostic Value of Platelet Aggregation Function in Patients with laryngeal Carcinoma. Int J Gen Med 2023; 16:5559-5566. [PMID: 38034899 PMCID: PMC10683666 DOI: 10.2147/ijgm.s428122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 10/18/2023] [Indexed: 12/02/2023] Open
Abstract
Background Laryngeal cancer was one of the most common malignancies of the head in those years. It has become one of the most common causes of death due to its high recurrence rate and high metastasis rate. It was well known that platelets, especially activated platelets, promote the proliferation, division, and invasion of tumor cells. Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet aggregation function in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet aggregation function in laryngeal cancer. Materials and Methods Between January 2015 and December 2016, we conducted a retrospective analysis of 203 patients who were diagnosed with laryngeal cancer consecutively. The patients were stratified by platelet aggregation function into two groups: low "adenosine diphosphate induced light transmittance aggregometry (ADP-induced LTA) ≤15.1" and high (ADP-induced LTA >15.1). Pathological tissues from different parts of the operation were collected and the pathologist determined the pathological type. We assessed the prognostic significance of platelet aggregation function using Kaplan-Meier curves and Cox regression. Results The low cohort had a significantly higher lymphocyte count than the high cohort. Compared with the high cohort, the low cohort had significantly lower levels of platelet-to-lymphocyte ratio (PLR), ADP-induced LTA, and Interleukins (IL)-6. The ADP-induced LTA (hazard ratio, 1.212; P <0.001) was independently related with 5-year overall survival rate. Conclusion Patients with ADP-induced LTA >15.1 experience poor outcomes. Platelet aggregation function, when elevated, could be a new prognostic indicator for laryngeal cancer.
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Affiliation(s)
- Minghua Li
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Jiawei Gui
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Hao Wang
- Department of Otolaryngology-Head and Neck Surgery, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210019, People’s Republic of China
| | - Jun An
- Department of Otolaryngology-Head and Neck Surgery, Xuzhou Central Hospital, Xuzhou, 221009, People’s Republic of China
| | - Ruoqing Wu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Xiaotong Liu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Bo Wu
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
| | - Hui Xiao
- Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China
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Verissimo DCA, Camillo-Andrade AC, Santos MDM, Sprengel SL, Zanine SC, Borba LAB, Carvalho PC, da G. Fischer JDS. Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas. PLoS One 2023; 18:e0290087. [PMID: 37967105 PMCID: PMC10651032 DOI: 10.1371/journal.pone.0290087] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 07/25/2023] [Indexed: 11/17/2023] Open
Abstract
Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes related to progression from grade 2 to grade 4 astrocytoma are already known, mRNA copies do not necessarily correlate with protein abundance and therefore could shadow further comprehension about this tumor's biology. This motivates us to seek for complementary strategies to study tumor progression at the protein level. Here we compare the proteomic profile of biopsies from patients with grade 2 (diffuse, n = 6) versus grade 4 astrocytomas (glioblastomas, n = 10) using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the 2- and 4-grade groups, respectively. Our results revealed seventy-four differentially abundant proteins (p < 0.01); we then shortlist those related to greater malignancy. We also describe molecular pathways distinctly activated in the two groups, such as differences in the organization of the extracellular matrix, decisive both in tumor invasiveness and in signaling for cell division, which, together with marked contrasts in energy metabolism, are determining factors in the speed of growth and dissemination of these neoplasms. The degradation pathways of GABA, enriched in the grade 2 group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to grade 4 tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups.
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Affiliation(s)
- Denildo C. A. Verissimo
- Laboratory for Structural and Computational Proteomics—Carlos Chagas Institute, Fiocruz Paraná, Curitiba, PR, Brazil
- Clinical Hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Amanda C. Camillo-Andrade
- Laboratory for Structural and Computational Proteomics—Carlos Chagas Institute, Fiocruz Paraná, Curitiba, PR, Brazil
| | - Marlon D. M. Santos
- Laboratory for Structural and Computational Proteomics—Carlos Chagas Institute, Fiocruz Paraná, Curitiba, PR, Brazil
| | - Sergio L. Sprengel
- Clinical Hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Simone C. Zanine
- Clinical Hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Luis A. B. Borba
- Clinical Hospital of the Federal University of Paraná, Curitiba, Paraná, Brazil
| | - Paulo C. Carvalho
- Laboratory for Structural and Computational Proteomics—Carlos Chagas Institute, Fiocruz Paraná, Curitiba, PR, Brazil
| | - Juliana de S. da G. Fischer
- Laboratory for Structural and Computational Proteomics—Carlos Chagas Institute, Fiocruz Paraná, Curitiba, PR, Brazil
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Balomenakis C, Papazoglou AS, Vlachopoulou D, Kartas A, Moysidis DV, Vouloagkas I, Tsagkaris C, Georgopoulos K, Samaras A, Karagiannidis E, Giannakoulas G. Risk of arterial thromboembolism, bleeding and mortality in atrial fibrillation patients with comorbid cancer: A systematic review and meta-analysis. Hellenic J Cardiol 2023; 74:65-73. [PMID: 37414144 DOI: 10.1016/j.hjc.2023.06.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 06/08/2023] [Accepted: 06/23/2023] [Indexed: 07/08/2023] Open
Abstract
AIMS Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer. METHODS Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used. RESULTS Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I2 = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I2 = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I2 = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk. CONCLUSION In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer.
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Affiliation(s)
- Charalampos Balomenakis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Andreas S Papazoglou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece; Athens Naval Hospital, Athens, Greece
| | - Dimitra Vlachopoulou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Anastasios Kartas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Dimitrios V Moysidis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Ioannis Vouloagkas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Christos Tsagkaris
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Konstantinos Georgopoulos
- Faculty of Engineering, School of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios Samaras
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - Efstratios Karagiannidis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
| | - George Giannakoulas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.
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Feka J, Jomrich G, Winkler D, Ilhan-Mutlu A, Kristo I, Paireder M, Rieder E, Bologheanu M, Asari R, Schoppmann SF. Platelets as a prognostic factor for patients with adenocarcinoma of the gastroesophageal junction. Langenbecks Arch Surg 2023; 408:351. [PMID: 37673810 PMCID: PMC10482770 DOI: 10.1007/s00423-023-03093-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 09/01/2023] [Indexed: 09/08/2023]
Abstract
OBJECTIVE The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with resectable adenocarcinomas of the gastroesophageal junction. BACKGROUND Platelet activation, quantified by PLT and elevated MPV, plays an essential part in the biological process of carcinogenesis and metastasis. An increased preoperative COP-MPV is associated with poor survival in various tumor entities. METHODS Data of 265 patients undergoing surgical resection for adenocarcinoma of the gastroesophageal junction were abstracted. COP-MPV score was defined for each patient. Utilizing univariate and multivariate Cox proportional hazard analyses, survival was determined. RESULTS In univariate analysis, elevated PLT (HR 3.58, 95% CI 2.61-4.80, p<0.001) and increased COP-MPV (HR 0.27, 95% CI 0.17-0.42, p<0.001 and HR 0.42, 95% CI 0.29-0.60, p<0.001) significantly correlated with shorter patients' overall and disease-free survival, for all 256 patients, as well as in the subgroups of neoadjuvantly treated (p<0.001) and primarily resected patients (p<0.001). COP-MPV remained a significant prognostic factor in multivariate analysis for OS. However, PLT alone showed significant diminished OS and DFS in all subgroups (p<0.001) in univariate and multivariate analysis. CONCLUSION PLT is a potent independent prognostic biomarker for survival in a large prospective cohort of patients with resectable adenocarcinoma of the gastroesophageal junction. Additionally, we confirm that the COP-MPV score is significantly associated with worse outcome in these patients, but has no benefit in comparison to PLT.
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Affiliation(s)
- Joy Feka
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Gerd Jomrich
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Daniel Winkler
- Department of Statistics and Operations Research, University of Vienna, Oskar Morgenstern Platz 1, 1090, Vienna, Austria
| | - Ayseguel Ilhan-Mutlu
- Department of Medicine 1, Comprehensive Cancer Center (CCC), Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Ivan Kristo
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Matthias Paireder
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Erwin Rieder
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Milena Bologheanu
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Reza Asari
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Sebastian F Schoppmann
- Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
- Upper-GI Unit, Department of Surgery, Division of General Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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20
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Xulu KR, Nweke EE, Augustine TN. Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches. Front Genet 2023; 14:1087432. [PMID: 37662839 PMCID: PMC10469897 DOI: 10.3389/fgene.2023.1087432] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 08/08/2023] [Indexed: 09/05/2023] Open
Abstract
The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1 and BRCA2, and hormone receptors. However, even within each subtype, heterogeneity that is driven by underlying evolutionary mechanisms is suggested to underlie poor response to therapy, variance in disease progression, recurrence, and relapse. Intratumoral heterogeneity highlights that the evolvability of tumor cells depends on interactions with cells of the tumor microenvironment. The complexity of the tumor microenvironment is being unraveled by recent advances in screening technologies such as high throughput sequencing; however, there remain challenges that impede the practical use of these approaches, considering the underlying biology of the tumor microenvironment and the impact of selective pressures on the evolvability of tumor cells. In this review, we will highlight the advances made thus far in defining the molecular heterogeneity in breast cancer and the implications thereof in diagnosis, the design and application of targeted therapies for improved clinical outcomes. We describe the different precision-based approaches to diagnosis and treatment and their prospects. We further propose that effective cancer diagnosis and treatment are dependent on unpacking the tumor microenvironment and its role in driving intratumoral heterogeneity. Underwriting such heterogeneity are Darwinian concepts of natural selection that we suggest need to be taken into account to ensure evolutionarily informed therapeutic decisions.
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Affiliation(s)
- Kutlwano Rekgopetswe Xulu
- School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Ekene Emmanuel Nweke
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tanya Nadine Augustine
- School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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21
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Anderson R, Rapoport BL, Steel HC, Theron AJ. Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer. Int J Mol Sci 2023; 24:11927. [PMID: 37569299 PMCID: PMC10418868 DOI: 10.3390/ijms241511927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/17/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023] Open
Abstract
Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.
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Affiliation(s)
- Ronald Anderson
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (B.L.R.); (H.C.S.); (A.J.T.)
| | - Bernardo L. Rapoport
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (B.L.R.); (H.C.S.); (A.J.T.)
- The Medical Oncology Centre of Rosebank, Johannesburg 2196, South Africa
| | - Helen C. Steel
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (B.L.R.); (H.C.S.); (A.J.T.)
| | - Annette J. Theron
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa; (B.L.R.); (H.C.S.); (A.J.T.)
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22
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Li H, Liu J, Yan S, Rao C, Wang L. Increased Platelet Distribution Width Predicts 3-Year Recurrence in Patients with Hepatocellular Carcinoma After Surgical Resection. Cancer Manag Res 2023; 15:501-509. [PMID: 37337478 PMCID: PMC10277002 DOI: 10.2147/cmar.s408548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/02/2023] [Indexed: 06/21/2023] Open
Abstract
Background Platelet distribution width (PDW) is a marker of platelet anisocytosis that increases with platelet activation. The clinical implications of PDW in HCC are not well-defined. This study aimed to determine whether PDW could predict recurrence in patients with HCC after resection. Methods Between January and December 2008, 471 patients with HCC were recruited retrospectively. The clinicopathological characteristics of patients with HCC were analyzed based on the relationship between the two PDW groups. Kaplan-Meier curves and multivariate Cox regression analyses were used to evaluate the relationship between PDW and disease-free survival (DFS). A novel nomogram was developed based on the identified independent risk factors. Its accuracy was evaluated using a calibration curve and concordance index. The predictive value was evaluated using a receiver operating characteristic (ROC) curve. Results PDW was significantly associated with direct bilirubin, total bilirubin, urea, and prothrombin time. Patients with PDW ≥ 17.1 were a significantly shorter DFS than those with PDW < 17.1 (17.98% vs 49.83%, p< 0.001). Multivariate analysis determined that alpha-fetoprotein (AFP), carcinoembryonic antigen, microvascular invasion (MVI), tumor size, and tumor number were the independent variables associated with DFS. Patients with PDW ≥ 17.1 had a hazard ratio of 1.381 (95% confidence interval: 1.069-1.783, p = 0.014) for DFS. AFP, PDW, MVI, tumor size, and tumor number were identified as preoperative independent risk factors for DFS and used to establish the nomogram. Calibration curve analysis revealed that the standard curve fitted well with the predicted curve. ROC curve analysis demonstrated the high efficiency of the nomogram. Conclusion Increased PDW may predict recurrence-free survival in patients with HCC. Our nomogram model also performed well in predicting patient prognoses.
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Affiliation(s)
- Huiming Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Jun Liu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Shaoying Yan
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Chunmei Rao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China
| | - Ling Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
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23
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Yoshimoto M, Kagawa S, Kajioka H, Taniguchi A, Kuroda S, Kikuchi S, Kakiuchi Y, Yagi T, Nogi S, Teraishi F, Shigeyasu K, Yoshida R, Umeda Y, Noma K, Tazawa H, Fujiwara T. Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma. Cancer Lett 2023:216260. [PMID: 37295551 DOI: 10.1016/j.canlet.2023.216260] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/01/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023]
Abstract
The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy.
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Affiliation(s)
- Masashi Yoshimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shunsuke Kagawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
| | - Hiroki Kajioka
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Atsuki Taniguchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shinji Kuroda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan
| | - Satoru Kikuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshihiko Kakiuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan
| | - Tomohiko Yagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shohei Nogi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Fuminori Teraishi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan
| | - Kunitoshi Shigeyasu
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Minimally Invasive Therapy Center, Okayama University Hospital, Okayama, Japan
| | - Ryuichi Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuhiro Noma
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroshi Tazawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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24
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Górnicki T, Bułdyś K, Zielińska D, Chabowski M. Direct-Acting Oral Anticoagulant Therapy in Cancer Patients-A Review. Cancers (Basel) 2023; 15:2697. [PMID: 37345034 PMCID: PMC10216040 DOI: 10.3390/cancers15102697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/21/2023] [Accepted: 05/08/2023] [Indexed: 06/23/2023] Open
Abstract
Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.
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Affiliation(s)
- Tomasz Górnicki
- Student Research Club No. 180, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (T.G.); (K.B.)
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland
| | - Kacper Bułdyś
- Student Research Club No. 180, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (T.G.); (K.B.)
| | - Dorota Zielińska
- Department of Surgery, 4th Military Teaching Hospital, 50-981 Wroclaw, Poland
| | - Mariusz Chabowski
- Department of Surgery, 4th Military Teaching Hospital, 50-981 Wroclaw, Poland
- Division of Anesthesiological and Surgical Nursing, Department of Nursing and Obstetrics, Faculty of Health Science, Wroclaw Medical University, 51-618 Wroclaw, Poland
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25
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Kawano T, Hisada Y, Grover SP, Schug WJ, Paul DS, Bergmeier W, Mackman N. Decreased Platelet Reactivity and Function in a Mouse Model of Human Pancreatic Cancer. Thromb Haemost 2023; 123:501-509. [PMID: 36716775 PMCID: PMC10820933 DOI: 10.1055/s-0043-1761419] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Cancer patients have increased thrombosis and bleeding compared with the general population. Cancer is associated with activation of both platelets and coagulation. Mouse models have been used to study the dysregulation of platelets and coagulation in cancer. We established a mouse model of pancreatic cancer in which tissue factor-expressing human pancreatic tumors (BxPC-3) are grown in nude mice. Tumor-bearing mice have an activated coagulation system and increased venous thrombosis compared to control mice. We also showed that tumor-derived, tissue factor-positive extracellular vesicles activated platelets ex vivo and in vivo. In this study, we determined the effect of tumors on a platelet-dependent arterial thrombosis model. Unexpectedly, we observed significantly reduced carotid artery thrombosis in tumor-bearing mice compared to controls. In addition, we observed significantly increased tail bleeding in tumor-bearing mice compared to controls. These results suggested that the presence of the tumor affected platelets. Indeed, tumor-bearing mice exhibited a significant decrease in platelet count and an increase in mean platelet volume and percentage of reticulated platelets, findings that are consistent with increased platelet turnover. Levels of the platelet activation marker platelet factor 4 were also increased in tumor-bearing mice. We also observed decreased platelet receptor expression in tumor-bearing mice and reduced levels of active αIIb/β3 integrin in response to PAR4 agonist peptide and convulxin in platelets from tumor-bearing mice compared with platelets from control mice. In summary, our study suggests that in tumor-bearing mice there is chronic platelet activation, leading to thrombocytopenia, decreased receptor expression, and impaired platelet adhesive function.
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Affiliation(s)
- Tomohiro Kawano
- Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
| | - Yohei Hisada
- Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
| | - Steven P. Grover
- Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
| | - Wyatt J. Schug
- Department of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, United States
| | - David S. Paul
- Department of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, United States
| | - Wolfgang Bergmeier
- Department of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, North Carolina, United States
| | - Nigel Mackman
- Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
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26
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Kassassir H, Papiewska-Pająk I, Kryczka J, Boncela J, Kowalska MA. Platelet-derived microparticles stimulate the invasiveness of colorectal cancer cells via the p38MAPK-MMP-2/MMP-9 axis. Cell Commun Signal 2023; 21:51. [PMID: 36882818 PMCID: PMC9990213 DOI: 10.1186/s12964-023-01066-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 02/04/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND Metastasis is the main cause of death in patients with colorectal cancer (CRC). Apart from platelets, platelet-derived microparticles (PMPs) are also considered important factors that can modify the activity of cancer cells. PMPs are incorporated by cancer cells and can also serve as intracellular signalling vesicles. PMPs are believed to affect cancer cells by upregulating their invasiveness. To date, there is no evidence that such a mechanism occurs in colorectal cancer. It has been shown that platelets can stimulate metalloproteases (MMPs) expression and activity via the p38MAPK pathway in CRC cells, leading to their elevated migratory potential. This study aimed to investigate the impact of PMPs on the invasive potential of CRC cells of various phenotypes via the MMP-2, MMP-9 and p38MAPK axis. METHODS We used various CRC cell lines, including the epithelial-like HT29 and the mesenchymal-like SW480 and SW620. Confocal imaging was applied to study PMP incorporation into CRC cells. The presence of surface receptors on CRC cells after PMP uptake was evaluated by flow cytometry. Transwell and scratch wound-healing assays were used to evaluate cell migration. The level of C-X-C chemokine receptor type 4 (CXCR4), MMP-2, and MMP-9 and the phosphorylation of ERK1/2 and p38MAPK were measured by western blot. MMP activity was determined using gelatine-degradation assays, while MMP release was evaluated by ELISA. RESULTS We found that CRC cells could incorporate PMPs in a time-dependent manner. Moreover, PMPs could transfer platelet-specific integrins and stimulate the expression of integrins already present on tested cell lines. While mesenchymal-like cells expressed less CXCR4 than epithelial-like CRC cells, PMP uptake did not increase its intensity. No significant changes in CXCR4 level either on the surface or inside CRC cells were noticed. Levels of cellular and released MMP-2 and MMP-9 were elevated in all tested CRC cell lines after PMP uptake. PMPs increased the phosphorylation of p38MAPK but not that of ERK1/2. Inhibition of p38MAPK phosphorylation reduced the PMP-induced elevated level and release of MMP-2 and MMP-9 as well as MMP-dependent cell migration in all cell lines. CONCLUSIONS We conclude that PMPs can fuse into both epithelial-like and mesenchymal-like CRC cells and increase their invasive potential by inducing the expression and release of MMP-2 and MMP-9 via the p38MAPK pathway, whereas CXCR4-related cell motility or the ERK1/2 pathway appears to not be affected by PMPs. Video Abstract.
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Affiliation(s)
- Hassan Kassassir
- Laboratory of Cellular Signaling, Institute of Medical Biology, Polish Academy of Science, Lodowa 106, Lodz, Poland.
| | - Izabela Papiewska-Pająk
- Laboratory of Cellular Signaling, Institute of Medical Biology, Polish Academy of Science, Lodowa 106, Lodz, Poland
| | - Jakub Kryczka
- Laboratory of Cellular Signaling, Institute of Medical Biology, Polish Academy of Science, Lodowa 106, Lodz, Poland
| | - Joanna Boncela
- Laboratory of Cellular Signaling, Institute of Medical Biology, Polish Academy of Science, Lodowa 106, Lodz, Poland
| | - M Anna Kowalska
- Laboratory of Cellular Signaling, Institute of Medical Biology, Polish Academy of Science, Lodowa 106, Lodz, Poland.,The Children's Hospital of Philadelphia, Philadelphia, PA, USA
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27
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Salazar-Valdivia FE, Valdez-Cornejo VA, Ulloque-Badaracco JR, Hernandez-Bustamante EA, Alarcón-Braga EA, Mosquera-Rojas MD, Garrido-Matta DP, Herrera-Añazco P, Benites-Zapata VA, Hernandez AV. Systemic Immune-Inflammation Index and Mortality in Testicular Cancer: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2023; 13:843. [PMID: 36899987 PMCID: PMC10000460 DOI: 10.3390/diagnostics13050843] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/25/2023] Open
Abstract
The systemic immune-inflammation index (SIII) is a marker studied in multiple types of urologic cancer. This systematic review evaluates the association between SIII values with overall survival (OS) and progression-free survival (PFS) in testicular cancer. We searched observational studies in five databases. The quantitative synthesis was performed using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The only measure of the effect was the hazard ratio (HR). A sensitivity analysis was performed according to the risk of bias in the studies. There were 833 participants in a total of 6 cohorts. We found that high SIII values were associated with worse OS (HR = 3.28; 95% CI 1.3-8.9; p < 0.001; I2 = 78) and PFS (HR = 3.9; 95% CI 2.53-6.02; p < 0.001; I2 = 0). No indication of small study effects was found in the association between SIII values and OS (p = 0.5301). High SIII values were associated with worse OS and PFS. However, further primary studies are suggested to enhance the effect of this marker in different outcomes of testicular cancer patients.
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Affiliation(s)
- Farley E. Salazar-Valdivia
- Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
- Sociedad Científica de Estudiantes de Medicina de la Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
| | - Valeria A. Valdez-Cornejo
- Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
- Sociedad Científica de Estudiantes de Medicina de la Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
| | | | - Enrique A. Hernandez-Bustamante
- Sociedad Científica de Estudiantes de Medicina de la Universidad Nacional de Trujillo, Trujillo 13011, Peru
- Grupo Peruano de Investigación Epidemiológica, Unidad para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima 15012, Peru
| | - Esteban A. Alarcón-Braga
- Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
- Sociedad Científica de Estudiantes de Medicina de la Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
| | - Melany D. Mosquera-Rojas
- Escuela de Medicina, Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
- Sociedad Científica de Estudiantes de Medicina de la Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
| | | | - Percy Herrera-Añazco
- Escuela de Medicina, Universidad Privada San Juan Bautista, Lima 15067, Peru
- Universidad Privada del Norte, Trujillo 13011, Peru
| | - Vicente A. Benites-Zapata
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima 14072, Peru
| | - Adrian V. Hernandez
- Unidad de Revisiones Sistemáticas y Meta-análisis, Guías de Práctica Clínica y Evaluaciones de Tecnología Sanitaria, Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima 15012, Peru
- Health Outcomes, Policy, and Evidence Synthesis Group, University of Connecticut School of Pharmacy, Mansfield, CT 06269, USA
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28
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Shi Q, Ji T, Tang X, Guo W. The role of tumor-platelet interplay and micro tumor thrombi during hematogenous tumor metastasis. Cell Oncol (Dordr) 2023; 46:521-532. [PMID: 36652166 DOI: 10.1007/s13402-023-00773-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND In addition to their pivotal roles in coagulation and thrombosis, platelets are crucial in tumor progression, with plenty of clinical and experimental data demonstrating that the interplay of platelets and tumor cells is essential for hematogenous tumor metastasis. After detach from primary sites, tumor cells intravasate into the blood circulation becoming circulating tumor cells and induce platelet activation, aggregation and encasement around tumor cells to form micro tumor thrombi, which create a permissive tumor microenvironment for metastasis. Platelets in micro tumor thrombi protect tumor cells from immune surveillance and anoikis (detachment-triggered apoptosis) through various pathways, which are significant for tumor cell survival in the bloodstream. Moreover, platelets can facilitate tumor metastasis by expediting epithelial-mesenchymal transition (EMT), adhesion to the endothelium, angiogenesis, tumor proliferation processes and platelet-derived microvesicle (PMV) formation. CONCLUSIONS Here, we provide a synopsis of the current understanding of the formation of micro tumor thrombi and the role of micro tumor thrombi in tumor hematogenous metastasis based on the tumor-platelet interplay. We also highlight potential therapeutic strategies targeting platelets for tumor treatment, including cancer-associated platelet-targeted nanomedicines.
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Affiliation(s)
- Qianyu Shi
- Department of Musculoskeletal Tumor, People's Hospital, Peking University, 100044, Beijing, China
- Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
| | - Tao Ji
- Department of Musculoskeletal Tumor, People's Hospital, Peking University, 100044, Beijing, China.
- Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China.
| | - Xiaodong Tang
- Department of Musculoskeletal Tumor, People's Hospital, Peking University, 100044, Beijing, China
| | - Wei Guo
- Department of Musculoskeletal Tumor, People's Hospital, Peking University, 100044, Beijing, China
- Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People's Republic of China
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Li Y, Wang H, Zhao Z, Yang Y, Meng Z, Qin L. Effects of the interactions between platelets with other cells in tumor growth and progression. Front Immunol 2023; 14:1165989. [PMID: 37153586 PMCID: PMC10158495 DOI: 10.3389/fimmu.2023.1165989] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 03/31/2023] [Indexed: 05/09/2023] Open
Abstract
It has been confirmed that platelets play a key role in tumorigenesis. Tumor-activated platelets can recruit blood cells and immune cells to migrate, establish an inflammatory tumor microenvironment at the sites of primary and metastatic tumors. On the other hand, they can also promote the differentiation of mesenchymal cells, which can accelerate the proliferation, genesis and migration of blood vessels. The role of platelets in tumors has been well studied. However, a growing number of studies suggest that interactions between platelets and immune cells (e.g., dendritic cells, natural killer cells, monocytes, and red blood cells) also play an important role in tumorigenesis and tumor development. In this review, we summarize the major cells that are closely associated with platelets and discuss the essential role of the interaction between platelets with these cells in tumorigenesis and tumor development.
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Çağlar R. The relationship of different preoperative inflammatory markers with the prognosis of gastric carcinoma. Asian J Surg 2023; 46:360-365. [PMID: 35589478 DOI: 10.1016/j.asjsur.2022.04.075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 03/15/2022] [Accepted: 04/21/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND It is aimed to determine the prognostic values of preoperative inflammatory biomarkers in patients undergoing curative surgery for gastric carcinoma and to contribute to the development of prognostic modeling. OBJECTIVE To investigate the effect of various different preoperative inflammatory markers on the prognosis of gastric carcinoma. MATERIAL AND METHOD The medical data and the mortality status of 91 patients who underwent total or subtotal gastrectomy operation for gastric carcinoma at Mersin City Training and Research Hospital between 2016 and 2020 were retrospectively reviewed from the hospital records and patient files. The patients' demographic characteristics, tumor location, histopathological diagnosis, pathological stage, tumor markers, and preoperative inflammatory and hematological markers were analyzed. Based on these data, tumor stage, metastatic lymph node ratio (MLR), lactate dehydrogenase albumin ratio (LAR), neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) were calculated. The relationship between these parameters and postoperative survival was analyzed. Statistical analyses were performed with IBM SPSS for Windows, version 17.0 (IBM Corporation, Armonk, New York, United States). RESULTS The correlation analysis of the parameters affecting survival showed that, in addition to an advanced tumor stage, inflammatory parameters like NLR, PLR, and LAR adversely affected survival. CONCLUSION Preoperative NLR, PLR, LAR, and advanced tumor stage may help determine the survival of gastric carcinoma patients. Multiple studies with larger series are needed on this subject.
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Affiliation(s)
- Recep Çağlar
- Mersin City Training and Research Hospital, Department of General Surgery/ Gastroenterological Surgery, Mersin, Turkey.
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An Overview of Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Canine Tumors: How Far Have We Come? Vet Sci 2022; 10:vetsci10010019. [PMID: 36669020 PMCID: PMC9865109 DOI: 10.3390/vetsci10010019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/23/2022] [Accepted: 12/24/2022] [Indexed: 12/31/2022] Open
Abstract
Historically, pre-clinical and clinical studies in human medicine have provided new insights, pushing forward the contemporary knowledge. The new results represented a motivation for investigators in specific fields of veterinary medicine, who addressed the same research topics from different perspectives in studies based on experimental and spontaneous animal disease models. The study of different pheno-genotypic contexts contributes to the confirmation of translational models of pathologic mechanisms. This review provides an overview of EMT and MET processes in both human and canine species. While human medicine rapidly advances, having a large amount of information available, veterinary medicine is not at the same level. This situation should provide motivation for the veterinary medicine research field, to apply the knowledge on humans to research in pets. By merging the knowledge of these two disciplines, better and faster results can be achieved, thus improving human and canine health.
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Ke Y, Ma Z, Ye H, Guan X, Xiang Z, Xia Y, Shi Q. Chlorogenic Acid-Conjugated Nanoparticles Suppression of Platelet Activation and Disruption to Tumor Vascular Barriers for Enhancing Drug Penetration in Tumor. Adv Healthc Mater 2022; 12:e2202205. [PMID: 36509084 DOI: 10.1002/adhm.202202205] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/25/2022] [Indexed: 12/14/2022]
Abstract
Hypercoagulation threatens the lives of cancer patients and cancer progression. Platelet overactivation attributes to the tumor-associated hypercoagulation and maintenance of the tumor endothelial integrity, leading to limited intratumoral perfusion of nanoagents into solid tumors in spite of the enhanced penetration and retention effect (EPR). Therefore, the clinical application of nanotherapeutics in solid cancer still faces great challenges. Herein, this work establishes platelet inhibiting nanoagents based on FeIII -doped C3 N4 coloaded with the chemotherapy drug and the antiplatelet drug chlorogenic acid (CA), further opening tumor vascular endothelial junctions, thereby disrupting the tumor vascular endothelial integrity, and enhancing drug perfusion. Moreover, CA not only damages the cancer cells but also potentiates the cytotoxicity induced by the chemotherapy drug doxorubicin, synergistically ablating the tumor tissue. Further, the introduction of CA relieves the original causes of the hypercoagulable state such as tissue factor (TF), thrombin, and matrix metalloproteinases (MMPs) secreted by cancer cells. It is anticipated that the hypercoagulation- and platelet-inhibition strategy by integration of phenolic acid CA into chemotherapy provides insights into platelet inhibition-assisted theranostics based on nanomedicines.
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Affiliation(s)
- Yue Ke
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.,School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Zhifang Ma
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
| | - Hongbo Ye
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
| | - Xinghua Guan
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
| | - Zehong Xiang
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.,School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yu Xia
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.,School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Qiang Shi
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.,School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
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Xulu KR, Augustine TN. Targeting Platelet Activation Pathways to Limit Tumour Progression: Current State of Affairs. Pharmaceuticals (Basel) 2022; 15:1532. [PMID: 36558983 PMCID: PMC9784118 DOI: 10.3390/ph15121532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
The association between cancer and a hypercoagulatory environment is well described. Thrombotic complications serve not only as a major mortality risk but the underlying molecular structure and function play significant roles in enhancing tumour progression, which is defined as the tumour's capacity to survive, invade and metastasise, amongst other hallmarks of the disease. The use of anticoagulant or antiplatelet drugs in cardiovascular disease lessens thrombotic effects, but the consequences on tumour progression require interrogation. Therefore, this review considered developments in the management of platelet activation pathways (thromboxane, ADP and thrombin), focusing on the use of Aspirin, Clopidogrel and Atopaxar, and their potential impacts on tumour progression. Published data suggested a cautionary tale in ensuring we adequately investigate not only drug-drug interactions but also those unforeseen reciprocal interactions between drugs and their targets within the tumour microenvironment that may act as selective pressures, enhancing tumour survival and progression.
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Affiliation(s)
- Kutlwano R. Xulu
- School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
| | - Tanya N. Augustine
- School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
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Hong Y, Chen X, Li G. Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection. BMC Surg 2022; 22:382. [DOI: 10.1186/s12893-022-01832-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/31/2022] [Indexed: 11/09/2022] Open
Abstract
Abstract
Background
Endoscopic submucosal dissection (ESD) is becoming increasingly popular as a treatment for precancerous lesions and early cancers of the stomach. However, there have been few studies on the factors associated with the recurrence of precancerous lesions after ESD.
Methods
To investigate the prognostic factors of gastric intraepithelial neoplasia, we retrospectively analyzed 115 patients who were treated with ESD between February 2018 and January 2020. Chi-square test and Fisher’s extract test were used to select factors for further investigation, and prognostic analysis was carried out with the Kaplan–Meier method and a Cox regression model.
Results
Platelet counts (P = 0.027) and albumin levels (P = 0.011) were both lower in patients with recurrence than in patients without recurrence of gastric mucosal atypical hyperplasia after ESD.
Conclusions
This study reveals that low platelet counts and albumin levels were probably unfavorable prognostic factors in mucosal atypical hyperplasia of the stomach.
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Han R, Tian Z, Jiang Y, Guan G, Wang X, Sun X, Yu Y, Jing X. Prognostic significance of the systemic immune inflammation index in patients with metastatic and unresectable pancreatic cancer. Front Surg 2022; 9:915599. [PMID: 36111233 PMCID: PMC9468225 DOI: 10.3389/fsurg.2022.915599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeSystemic inflammatory markers may be predictors of the survival rate of patients with pancreatic cancer (PC). The aim of this work was to investigate the prognostic value of markers, mainly the systemic immune inflammation index (SII), in patients with metastatic and unresectable PC and to explore the relationship between markers and liver metastasis.MethodsRecords of patients with metastatic and unresectable PC at the Affiliated Hospital of Qingdao University from January 2000 to December 2019 and who were followed until December 2020 were retrospectively analyzed. Clinical data and laboratory indexes were collected, and cut-off values for inflammatory markers were determined using median values. The Cox proportional hazard model was used to analyze the prognostic value of the markers through univariate and multivariate survival analysis.ResultsAll 253 patients met the inclusion criteria, and 102 (42.0%) patients had liver metastasis. The patients were divided into a high SII group and a low SII group, and the cut-off value was 533. In the multivariate analysis, high SII (HR = 2.151; p < 0.001), chemotherapy (HR = 0.546; p < 0.001), lymph node metastasis (HR = 4.053; p < 0.001), and distant metastasis (HR = 1.725; p = 0.001) were independent risk markers of overall survival (OS). The level of markers, mainly SII, PLR and NLR, were higher in patients with liver metastasis.ConclusionsA high level of SII is an independent risk factor for short overall survival of patients with metastatic and unresectable PC. Patients with a high level of the inflammatory markers SII, PLR, and NLR, may be more prone to early liver metastasis.
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Affiliation(s)
- Rongshuang Han
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zibin Tian
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yueping Jiang
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ge Guan
- Liver Disease Center Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaowei Wang
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xueguo Sun
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanan Yu
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xue Jing
- Gastroenterology Department, The Affiliated Hospital of Qingdao University, Qingdao, China
- Correspondence: Xue Jing
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Wang W, Tong Y, Sun S, Tan Y, Shan Z, Sun F, Jiang C, Zhu Y, Zhang J. Predictive value of NLR and PLR in response to preoperative chemotherapy and prognosis in locally advanced gastric cancer. Front Oncol 2022; 12:936206. [PMID: 36110962 PMCID: PMC9468320 DOI: 10.3389/fonc.2022.936206] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose Pretreatment neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios are markers of systemic inflammation. In patients with locally advanced gastric cancer (GC), the utility of these ratios in predicting tumor regression grade (TRG) after neoadjuvant chemotherapy (NCT) remains unclear. Methods This retrospective study examined 283 locally advanced GC patients who underwent NCT and radical surgery. The receiver operating characteristic (ROC) curve analysis and the Youden index were applied to identify optimal NLR/PLR cutpoints. The Kaplan–Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Univariate/multivariate analyses were conducted by the logistic regression method. Results TRG grade proved significantly worse in patients with high values of both NLR and PLR whether in univariate (OR = 3.457; p = 0.044) or multivariate (OR = 6.876; p = 0.028) analysis. The degree of tumor differentiation was an independent predictive factor for TRG (OR = 2.874; p = 0.037) in multivariate analysis. In the subgroup analyses, NLR predicted OS (p = 0.04) and DFS (p = 0.03) in female patients, whereas PLR was predictive of both OS (p = 0.026) and DFS (p = 0.018) in patients with clinical TNM stage 3 disease and dissected lymph node counts <28. PLR similarly predicted OS in patients <65 years old (p = 0.049), those with positive lymph nodes (p = 0.021), or those with moderate or poorly differentiated tumors (p = 0.049). Conclusion Pretreatment NLR and PLR together serve to independently predict TRG after NCT and surgery in patients with locally advanced GC. Screening for patients with high NLR and PLR values may allow them to benefit upfront from alternatives to NCT.
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Affiliation(s)
- Wentao Wang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Shulan Sun
- Department of Central Laboratory, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Fan Sun
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Chengyao Jiang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yanmei Zhu
- Department of Pathology, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
- *Correspondence: Jianjun Zhang, ; Yanmei Zhu,
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
- *Correspondence: Jianjun Zhang, ; Yanmei Zhu,
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Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis. Int J Mol Sci 2022; 23:ijms23179596. [PMID: 36076991 PMCID: PMC9455756 DOI: 10.3390/ijms23179596] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 11/21/2022] Open
Abstract
Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.
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Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis. J Clin Gastroenterol 2022; 56:e293-e302. [PMID: 35316225 DOI: 10.1097/mcg.0000000000001693] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/12/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION AND AIM The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC. METHODS We searched for PubMed and EMBASE through September 2021. RESULTS Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64). CONCLUSION Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.
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Wang L, Wang X, Guo E, Mao X, Miao S. Emerging roles of platelets in cancer biology and their potential as therapeutic targets. Front Oncol 2022; 12:939089. [PMID: 35936717 PMCID: PMC9355257 DOI: 10.3389/fonc.2022.939089] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 06/29/2022] [Indexed: 12/15/2022] Open
Abstract
The main role of platelets is to control bleeding and repair vascular damage via thrombosis. They have also been implicated to promote tumor metastasis through platelet-tumor cell interactions. Platelet-tumor cell interactions promote tumor cell survival and dissemination in blood circulation. Tumor cells are known to induce platelet activation and alter platelet RNA profiles. Liquid biopsies based on tumor-educated platelet biomarkers can detect tumors and correlate with prognosis, personalized therapy, treatment monitoring, and recurrence prediction. Platelet-based strategies for cancer prevention and tumor-targeted therapy include developing drugs that target platelet receptors, interfere with the release of platelet particles, inhibit platelet-specific enzymes, and utilize platelet-derived “nano-platelets” as a targeted drug delivery platform for tumor therapy. This review elaborates on platelet-tumor cell interactions and the molecular mechanisms and discusses future research directions for platelet-based liquid biopsy techniques and platelet-targeted anti-tumor strategies.
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Affiliation(s)
- Lei Wang
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xueying Wang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Erliang Guo
- Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xionghui Mao
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
- *Correspondence: Xionghui Mao, ; Susheng Miao,
| | - Susheng Miao
- Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China
- *Correspondence: Xionghui Mao, ; Susheng Miao,
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Parvin MS, Hrubša M, Fadraersada J, Carazo A, Karlíčková J, Cahlíková L, Chlebek J, Macáková K, Mladěnka P. Can Isoquinoline Alkaloids Affect Platelet Aggregation in Whole Human Blood? Toxins (Basel) 2022; 14:toxins14070491. [PMID: 35878229 PMCID: PMC9324755 DOI: 10.3390/toxins14070491] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/07/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023] Open
Abstract
Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.
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Affiliation(s)
- Mst Shamima Parvin
- The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.S.P.); (J.K.); (L.C.); (J.C.); (K.M.)
| | - Marcel Hrubša
- The Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.H.); (J.F.); (A.C.)
| | - Jaka Fadraersada
- The Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.H.); (J.F.); (A.C.)
| | - Alejandro Carazo
- The Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.H.); (J.F.); (A.C.)
| | - Jana Karlíčková
- The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.S.P.); (J.K.); (L.C.); (J.C.); (K.M.)
| | - Lucie Cahlíková
- The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.S.P.); (J.K.); (L.C.); (J.C.); (K.M.)
| | - Jakub Chlebek
- The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.S.P.); (J.K.); (L.C.); (J.C.); (K.M.)
| | - Kateřina Macáková
- The Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.S.P.); (J.K.); (L.C.); (J.C.); (K.M.)
| | - Přemysl Mladěnka
- The Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic; (M.H.); (J.F.); (A.C.)
- Correspondence: ; Tel.: +420-495-067-295
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Wang YT, Kuo LT, Weng HH, Hsu CM, Tsai MS, Chang GH, Lee YC, Huang EI, Tsai YT. Systemic Immun e–Inflammation Index as a Predictor for Head and Neck Cancer Prognosis: A Meta-Analysis. Front Oncol 2022; 12:899518. [PMID: 35814369 PMCID: PMC9263088 DOI: 10.3389/fonc.2022.899518] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/26/2022] [Indexed: 12/24/2022] Open
Abstract
Background Studies have reported inconsistent results regarding the prognostic value of the systemic immune–inflammation index (SII) in head and neck cancer (HNC). Thus, the present meta-analysis assessed the literature on the prognostic value of SII in those with HNC. Methods The Cochrane Library, EMBASE, and PubMed databases were searched, and study methodological quality was assessed using the Newcastle–Ottawa quality assessment scale. To determine the association of the SII with survival outcomes, pooled hazard ratios (HRs) as well as the associated 95% confidence intervals (CIs) were used. To assess the associations of the SII with clinicopathological features, the odds ratios (ORs) and corresponding 95% CIs were considered. Begg’s funnel plot and Egger’s linear regression test were used to assess publication bias. Results A total of 12 studies that together enrolled 4369 patients with HNC were analyzed. In the pooled results, a high pretreatment SII was correlated with poorer overall survival (HR = 2.09, 95% CI = 1.62–2.70, p < 0.001), disease-free survival (HR = 2.79, 95% CI = 1.99−3.89, p < 0.001), and progression-free survival (HR = 1.80, 95% CI = 1.30−2.48, p < 0.001). A stratified analysis indicated that SII for overall survival was applicable regardless of tumor site, treatment modality, overall stage, sample size, SII cutoff, and method for determining the SII cutoff. Furthermore, a high SII was correlated with a more advanced T classification (OR = 1.14, 95% CI = 1.09–1.18, p < 0.001) and nodal metastasis (OR = 1.55, 95% CI = 1.18–2.05, p = 0.002) in patients with HNC. Conclusions An elevated pretreatment SII predicts more advanced tumor and nodal status and poorer survival outcomes in cases of HNC. Because the measurement of SII is convenient and its use is cost-effective, we suggest that it can be applied by clinicians in the management of HNC.
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Affiliation(s)
- Yun-Ting Wang
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Liang-Tseng Kuo
- Division of Sports Medicine, Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Hsu-Huei Weng
- Department of Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Cheng-Ming Hsu
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ming-Shao Tsai
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Geng-He Chang
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yi-Chan Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ethan I. Huang
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Te Tsai
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- *Correspondence: Yao-Te Tsai,
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Strasenburg W, Jóźwicki J, Durślewicz J, Kuffel B, Kulczyk MP, Kowalewski A, Grzanka D, Drewa T, Adamowicz J. Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy. Front Oncol 2022; 12:909767. [PMID: 35814405 PMCID: PMC9259835 DOI: 10.3389/fonc.2022.909767] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
Tumor cells have the ability to induce platelet activation and aggregation. This has been documented to be involved in tumor progression in several types of cancers, such as lung, colon, breast, pancreatic, ovarian, and brain. During the process, platelets protect circulating tumor cells from the deleterious effects of shear forces, shield tumor cells from the immune system, and provide growth factors, facilitating metastatic spread and tumor growth at the original site as well as at the site of metastasis. Herein, we present a wider view on the induction of platelet aggregation by specific factors primarily developed by cancer, including coagulation factors, adhesion receptors, growth factors, cysteine proteases, matrix metalloproteinases, glycoproteins, soluble mediators, and selectins. These factors may be presented on the surface of tumor cells as well as in their microenvironment, and some may trigger more than just one simple receptor-ligand mechanism. For a better understanding, we briefly discuss the physiological role of the factors in the platelet activation process, and subsequently, we provide scientific evidence and discuss their potential role in the progression of specific cancers. Targeting tumor cell-induced platelet aggregation (TCIPA) by antiplatelet drugs may open ways to develop new treatment modalities. On the one hand, it may affect patients' prognosis by enhancing known therapies in advanced-stage tumors. On the other hand, the use of drugs that are mostly easily accessible and widely used in general practice may be an opportunity to propose an unparalleled antitumor prophylaxis. In this review, we present the recent discoveries of mechanisms by which cancer cells activate platelets, and discuss new platelet-targeted therapeutic strategies.
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Affiliation(s)
- Wiktoria Strasenburg
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Jakub Jóźwicki
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Justyna Durślewicz
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Błażej Kuffel
- Department of General and Oncological Urology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - Martyna Parol Kulczyk
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Adam Kowalewski
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Dariusz Grzanka
- Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Tomasz Drewa
- Department of General and Oncological Urology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland
| | - Jan Adamowicz
- Department of General and Oncological Urology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland
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Bergstrand J, Miao X, Srambickal CV, Auer G, Widengren J. Fast, streamlined fluorescence nanoscopy resolves rearrangements of SNARE and cargo proteins in platelets co-incubated with cancer cells. J Nanobiotechnology 2022; 20:292. [PMID: 35729633 PMCID: PMC9210740 DOI: 10.1186/s12951-022-01502-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/07/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Increasing evidence suggests that platelets play a central role in cancer progression, with altered storage and selective release from platelets of specific tumor-promoting proteins as a major mechanism. Fluorescence-based super-resolution microscopy (SRM) can resolve nanoscale spatial distribution patterns of such proteins, and how they are altered in platelets upon different activations. Analysing such alterations by SRM thus represents a promising, minimally invasive strategy for platelet-based diagnosis and monitoring of cancer progression. However, broader applicability beyond specialized research labs will require objective, more automated imaging procedures. Moreover, for statistically significant analyses many SRM platelet images are needed, of several different platelet proteins. Such proteins, showing alterations in their distributions upon cancer progression additionally need to be identified. RESULTS A fast, streamlined and objective procedure for SRM platelet image acquisition, analysis and classification was developed to overcome these limitations. By stimulated emission depletion SRM we imaged nanoscale patterns of six different platelet proteins; four different SNAREs (soluble N-ethylmaleimide factor attachment protein receptors) mediating protein secretion by membrane fusion of storage granules, and two angiogenesis regulating proteins, representing cargo proteins within these granules coupled to tumor progression. By a streamlined procedure, we recorded about 100 SRM images of platelets, for each of these six proteins, and for five different categories of platelets; incubated with cancer cells (MCF-7, MDA-MB-231, EFO-21), non-cancer cells (MCF-10A), or no cells at all. From these images, structural similarity and protein cluster parameters were determined, and probability functions of these parameters were generated for the different platelet categories. By comparing these probability functions between the categories, we could identify nanoscale alterations in the protein distributions, allowing us to classify the platelets into their correct categories, if they were co-incubated with cancer cells, non-cancer cells, or no cells at all. CONCLUSIONS The fast, streamlined and objective acquisition and analysis procedure established in this work confirms the role of SNAREs and angiogenesis-regulating proteins in platelet-mediated cancer progression, provides additional fundamental knowledge on the interplay between tumor cells and platelets, and represent an important step towards using tumor-platelet interactions and redistribution of nanoscale protein patterns in platelets as a basis for cancer diagnostics.
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Affiliation(s)
- Jan Bergstrand
- Department of Applied Physics, Experimental Biomolecular Physics, Albanova Univ Center, Royal Institute of Technology (KTH), 106 91, Stockholm, Sweden
| | - Xinyan Miao
- Department of Applied Physics, Experimental Biomolecular Physics, Albanova Univ Center, Royal Institute of Technology (KTH), 106 91, Stockholm, Sweden
| | - Chinmaya Venugopal Srambickal
- Department of Applied Physics, Experimental Biomolecular Physics, Albanova Univ Center, Royal Institute of Technology (KTH), 106 91, Stockholm, Sweden
| | - Gert Auer
- Department of Oncology-Pathology, K7, Z1:00, Karolinska University Hospital, Karolinska Institutet, 171 76, Stockholm, Sweden
| | - Jerker Widengren
- Department of Applied Physics, Experimental Biomolecular Physics, Albanova Univ Center, Royal Institute of Technology (KTH), 106 91, Stockholm, Sweden.
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Jarmuzek P, Kot M, Defort P, Stawicki J, Komorzycka J, Nowak K, Tylutka A, Zembron-Lacny A. Prognostic Values of Combined Ratios of White Blood Cells in Glioblastoma: A Retrospective Study. J Clin Med 2022; 11:3397. [PMID: 35743468 PMCID: PMC9225636 DOI: 10.3390/jcm11123397] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/02/2022] [Accepted: 06/07/2022] [Indexed: 12/20/2022] Open
Abstract
In some malignant tumours, the changes in neutrophil counts in relation to other blood cells are connected with unfavourable prognosis. Nevertheless, the prognostic value of the combinations of the haematological components in glioblastoma (GBM) remains under dispute. The clinical significance of the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) was investigated in our study. We retrospectively studied 358 patients (males n = 195; females n = 163) aged 59.9 ± 13.5 yrs with newly diagnosed glioma and admitted to the Neurosurgery Centre. Routine blood tests and clinical characteristics were recorded within the first hour of hospital admission. The inflammatory variables: NLR, SII and SIRI exceeded the reference values and were significantly elevated in Grade 3 and Grade 4 tumour. The Cox model analysis showed that the age ≥ 63 years, NLR ≥ 4.56 × 103/µL, SII ≥ 2003 × 103/µL and SIRI ≥ 3.03 × 103/µL significantly increased the risk of death in Grade 4 tumour patients. In the inflammatory variables, NLR demonstrated the highest impact on the survival time (HR 1.56; 95% CI 1.145-2.127; p = 0.005). In the first Polish study including GBM patients, the age in relation to simple parameters derived from complete blood cell count were found to have prognostic implications in the survival rate.
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Affiliation(s)
- Pawel Jarmuzek
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Marcin Kot
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Piotr Defort
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Jakub Stawicki
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Julia Komorzycka
- Student Research Group, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (J.K.); (K.N.)
| | - Karol Nowak
- Student Research Group, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (J.K.); (K.N.)
| | - Anna Tylutka
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (A.T.); (A.Z.-L.)
| | - Agnieszka Zembron-Lacny
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (A.T.); (A.Z.-L.)
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Yan J, Liu X, Wu F, Ge C, Ye H, Chen X, Wei Y, Zhou R, Duan S, Zhu R, Zheng Y, Yin L. Platelet Pharmacytes for the Hierarchical Amplification of Antitumor Immunity in Response to Self-Generated Immune Signals. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2109517. [PMID: 35388551 DOI: 10.1002/adma.202109517] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 04/02/2022] [Indexed: 05/24/2023]
Abstract
Systemic immunosuppression mediated by tumor-derived exosomes is an important cause for the resistance of immune checkpoint blockade (ICB) therapy. Herein, self-adaptive platelet (PLT) pharmacytes are engineered to mediate cascaded delivery of exosome-inhibiting siRNA and anti-PD-L1 (aPDL1) toward synergized antitumor immunity. In the pharmacytes, polycationic nanocomplexes (NCs) assembled from Rab27 siRNA (siRab) and a membrane-penetrating polypeptide are encapsulated inside the open canalicular system of PLTs, and cytotoxic T lymphocytes (CTLs)-responsive aPDL1 nanogels (NGs) are covalently backpacked on the PLT surface. Upon systemic administration, the pharmacytes enable prolonged blood circulation and active accumulation to tumors, wherein PLTs are activated to liberate siRab NCs, which efficiently transfect tumor cells, silence Rab27a, and inhibit exosome secretion. The immunosuppression is thus relieved, leading to the activation, proliferation, and tumoral infiltration of cytotoxic T cells, which trigger latent aPDL1 release. As such, the competitive aPDL1 exhaustion by PD-L1-expressing exosomes is minimized to sensitize ICB. Synergistically, siRab and aPDL1 induce strong antitumor immunological response and memory against syngeneic murine melanoma. This study reports a bioinspired mechanism to resolve the blood circulation/cell internalization contradiction of polycationic siRNA delivery systems, and renders an enlightened approach for the spatiotemporal enhancement of antitumor immunity.
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Affiliation(s)
- Jing Yan
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Xun Liu
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Fan Wu
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Chenglong Ge
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Huan Ye
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Xingye Chen
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Yuansong Wei
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Renxiang Zhou
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
| | - Shanzhou Duan
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Rongying Zhu
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Yiran Zheng
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Lichen Yin
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, 215123, China
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Jin X, Wang K, Shao X, Huang J. Prognostic implications of the peripheral platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in predicting pathologic complete response after neoadjuvant chemotherapy in breast cancer patients. Gland Surg 2022; 11:1057-1066. [PMID: 35800742 PMCID: PMC9253186 DOI: 10.21037/gs-22-244] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 05/18/2022] [Indexed: 10/20/2023]
Abstract
BACKGROUND The inflammatory response is extremely important in tumor progression, and it is very difficult to identify prognostic indicators for neoadjuvant therapy in breast cancer patients. The aim of this study was to mine the potential prognostic significance of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer patients receiving anthracycline- or taxane-based neoadjuvant chemotherapy (NACT). METHODS A total of 67 women diagnosed with breast cancer who received neoadjuvant therapy were enrolled in the study. Before starting NACT, the PLR and NLR were calculated. The optimal cutoff value was calculated using receiver operating characteristic (ROC) curve analyses, which indicated that 106.3 and 2.464 were the best cutoff values for the PLR and NLR, respectively. The optimal cutoff values for them were used to divide patients into low and high NLR groups and low and high PLR groups. Independent prognostic biomarkers and the value of PLR and NLR were assessed. The connection between the NLR/PLR and pathologic complete response (pCR), together with other clinical/pathological factors was evaluated. RESULTS Logistic regression model analyses revealed that patients with a high PLR correlated remarkably with better pCR than those with a low PLR. The results indicated that by using the cutoff value of 106.3, PLR had prognostic significance. However, there was no significant difference in NLR if analyzed separately. By combining PLR and NLR, the NLRhigh and PLRhigh subgroups achieved a significantly higher rate of pCR than the NLRIow/PLRIow subgroup [odds ratio (OR) 0.153, 95% confidence interval (CI): 0.068 to 0.876, P=0.008]. Therefore, the combination of NLRhigh/PLRhigh was an independent prognostic factor different from others, such as PLR, Ki-67, and chemotherapy regimen. CONCLUSIONS The PLR may serve as a potential marker of the efficacy of neoadjuvant therapy in breast cancer, enabling oncologists to intervene earlier. Peripheral blood NLR and PLR can reflect the immune status of patients. Indicating that an immunogenic phenotype is a good predictor of chemotherapy response and that combined studies can better identify immunophenotypes in patients.
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Affiliation(s)
- Xiaoyan Jin
- Department of Breast Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Department of Surgical Oncology, Municipal Hospital Affiliated to Taizhou University, Taizhou, China
| | - Ke Wang
- Department of Breast Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Shao
- Department of Breast Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Huang
- Department of Breast Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Zhang H, Xu Z, Zhang J, Wei D, Liu K, Hu W, Wang J. Disordered serum essential element levels are associated with increased risk of kidney tumors. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:31675-31685. [PMID: 35013964 DOI: 10.1007/s11356-021-18201-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 12/14/2021] [Indexed: 06/14/2023]
Abstract
Essential elements play vital roles in the regulation of carcinogenesis. We aimed to investigate the relationship between essential elements and kidney tumors. This study included 72 healthy individuals and 100 kidney tumor patients. The concentrations of cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), selenium (Se), and zinc (Zn) were determined by inductively coupled plasma mass spectrometry. The random forest model was used to evaluate the importance of each variable by using the randomForest package. The associations between essential elements and clinical tumor characteristics were examined by the Mann-Whitney U-test, and the log-rank test was used to assess the Kaplan-Meier curves. The levels of Co, Cr, Fe, Mn, Ni, and Zn in patients with kidney tumors were significantly lower. In the random forest model, the top two metallic features were Co and Zn. The Kaplan-Meier curve showed that patients with lower Co, Se, and Zn levels exhibited lower progression-free survival. In summary, this study gathered evidence that disordered essential elements are associated with kidney tumors and thus opens a new path to elucidate the etiology of kidney tumors from the perspective of environmental health and safety.
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Affiliation(s)
- Hui Zhang
- Department of Urology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China
| | - Zhipeng Xu
- Department of Urology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China
- Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Organ Transplantation and Nephrosis, Shandong Institute of Nephrology, Jinan, 250013, Shandong, China
| | - Jie Zhang
- The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, China
- Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Dan Wei
- Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan, 250013, Shandong, China
| | - Kai Liu
- Department of Urology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China
| | - Wenxin Hu
- Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Organ Transplantation and Nephrosis, Shandong Institute of Nephrology, Jinan, 250013, Shandong, China
| | - Jianning Wang
- Department of Urology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China.
- Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Organ Transplantation and Nephrosis, Shandong Institute of Nephrology, Jinan, 250013, Shandong, China.
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Campello E, Bosh F, Simion C, Spiezia L, Simioni P. Mechanisms of thrombosis in pancreatic ductal adenocarcinoma. Best Pract Res Clin Haematol 2022; 35:101346. [DOI: 10.1016/j.beha.2022.101346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/19/2022] [Indexed: 11/29/2022]
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Le Chapelain O, Ho-Tin-Noé B. Intratumoral Platelets: Harmful or Incidental Bystanders of the Tumor Microenvironment? Cancers (Basel) 2022; 14:cancers14092192. [PMID: 35565321 PMCID: PMC9105443 DOI: 10.3390/cancers14092192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/23/2022] [Accepted: 04/25/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary The tumor microenvironment (TME) is the complex and heterogenous ecosystem of solid tumors known to influence their growth and their progression. Besides tumor cells, the TME comprises a variety of host-derived cell types, ranging from endothelial cells to fibroblasts and immune cells. Clinical and experimental data are converging to indicate that platelets, originally known for their fundamental hemostatic function, also participate in tumor development and shaping of the TME. Considering the abundance of antiplatelet drugs, understanding if and how platelets contribute to the TME may lead to new therapeutic tools for improved cancer prevention and treatments. Abstract The tumor microenvironment (TME) has gained considerable interest because of its decisive impact on cancer progression, response to treatment, and disease recurrence. The TME can favor the proliferation, dissemination, and immune evasion of cancer cells. Likewise, there is accumulating evidence that intratumoral platelets could favor the development and aggressiveness of solid tumors, notably by influencing tumor cell phenotype and shaping the vascular and immune TME components. Yet, in contrast to other tumor-associated cell types like macrophages and fibroblasts, platelets are still often overlooked as components of the TME. This might be due, in part, to a deficit in investigating and reporting the presence of platelets in the TME and its relationships with cancer characteristics. This review summarizes available evidence from clinical and animal studies supporting the notion that tumor-associated platelets are not incidental bystanders but instead integral and active components of the TME. A particular emphasis is given to the description of intratumoral platelets, as well as to the functional consequences and possible mechanisms of intratumoral platelet accumulation.
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Jin J, Wu G, Ruan C, Ling H, Zheng X, Ying C, Zhang Y. Preoperative platelet distribution width-to-platelet ratio combined with serum thyroglobulin may be objective and popularizable indicators in predicting papillary thyroid carcinoma. J Clin Lab Anal 2022; 36:e24443. [PMID: 35441746 PMCID: PMC9169195 DOI: 10.1002/jcla.24443] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/02/2022] [Accepted: 04/06/2022] [Indexed: 11/30/2022] Open
Abstract
Objectives The incidence of papillary thyroid carcinoma (PTC) has increased more rapidly than that of any other cancer type in China. Early indicators with high sensitivity and specificity during diagnosis are required. To date, there has been a paucity of studies investigating the relationship between preoperative platelet distribution width‐to‐platelet count ratio (PPR) and PTC. This study thus aimed to assess the diagnostic value of PPR combined with serum thyroglobulin (Tg) in patients with PTC. Methods A total of 1001 participants were included in our study. 876 patients who underwent surgery for nodular goiter were divided into the PTC group or benign thyroid nodule (BTN) group according to pathology reports, and 125 healthy controls (HCs) were included. Preoperative hemogram parameters and serum Tg levels were compared among three groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of PPR combined with serum Tg for diagnosing PTC. Results Platelet distribution width (PDW) and PPR levels were higher in the PTC group than in the BTN and HC groups (both p < 0.05) but did not significantly differ between the BTN and HC groups. PDW and PPR levels significantly differed in the presence/absence of lymph node metastasis, the presence/absence of capsule invasion (p = 0.005), and TNM stages (p < 0.001). Multivariable analyses indicated that high serum Tg levels [adjusted odds ratio (OR), 1.007; 95% confidence interval (CI), 1.004–1.009; p < 0.001], high neutrophil‐to‐lymphocyte ratio (NLR,adjusted OR, 1.928; 95% CI, 1.619–2.295; p < 0.001), and high PPR (adjusted OR, 1.378; 95% CI, 1.268–1.497; p < 0.001) were independent risk factors for PTC. In ROC analysis, the areas under the curves (AUCs) of serum Tg, PDW, PPR, and NLR for predicting PTC were 0.603, 0.610, 0.706, and 0.685, respectively. PPR combined with serum Tg (PPR + Tg) had a higher diagnostic value (AUC, 0.738; sensitivity, 60%; specificity, 74.7%) compared with PDW + Tg (AUC, 0.656; sensitivity, 64.4%; specificity, 59.9%) and NLR + Tg (AUC, 0.714; sensitivity, 61.6%; specificity, 71.1%). Conclusions Preoperative PPR combined with serum Tg may be objective and popularizable indicators for effective predicting PTC.
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Affiliation(s)
- Jin Jin
- The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Guihua Wu
- The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Chengwei Ruan
- Department of Proctology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Hongwei Ling
- Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xueman Zheng
- The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Changjiang Ying
- Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Ying Zhang
- The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China
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