Author
Siamack Sabrkhany
Other affiliations: Maastricht University Medical Centre
Bio: Siamack Sabrkhany is an academic researcher from Maastricht University. The author has contributed to research in topics: Platelet & Cancer. The author has an hindex of 8, co-authored 13 publications receiving 320 citations. Previous affiliations of Siamack Sabrkhany include Maastricht University Medical Centre.
Topics: Platelet, Cancer, Medicine, Tyrosine-kinase inhibitor, Internal medicine
Papers
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TL;DR: The role of platelets in tumor angiogenesis and growth is discussed and their potential significance in malignancies is suggested, with the view that local adhesion and activation of blood platelets and dysregulation of coagulation represent underestimated pathways in the progression of cancer.
150 citations
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TL;DR: The role of stromal cells in the resistance to anti-angiogenic drugs is described and possible strategies to overcome resistance and enhance the efficacy of angiostatic therapy are discussed.
78 citations
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TL;DR: It is demonstrated that the platelet proteome of patients with early-stage lung or head of pancreas cancer differs considerably compared to that of healthy individuals of matched sex and age and after surgical resection of the tumor.
55 citations
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TL;DR: Multiple platelet features, including platelet count, volume and protein content, were significantly changed in lung and head of pancreas cancer patients, and a cancer type-specific combination of these platelets features can be used to discriminate between patients with early-stage cancer and healthy individuals.
42 citations
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TL;DR: In this article , a tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types with 99% specificity in asymptomatic controls.
23 citations
Cited by
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TL;DR: Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types, which presents interesting new targets for anticancer therapy.
3,486 citations
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2,777 citations
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TL;DR: The extrinsic regulation of angiogenesis by the tumour microenvironment is discussed, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.
Abstract: Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.
1,145 citations
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TL;DR: Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time window.
Abstract: Angiogenesis is defined as the formation of new blood vessels from preexisting vessels and has been characterized as an essential process for tumor cell proliferation and viability. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, alone or in combination with chemotherapy or other targeted therapies. But this success had only limited impact on overall survival of cancer patients and rarely resulted in durable responses. Given the recent success of immunotherapies, combinations of anti-angiogenics with immune checkpoint blockers have become an attractive strategy. However, implementing such combinations will require a better mechanistic understanding of their interaction. Due to overexpression of pro-angiogenic factors in tumors, their vasculature is often tortuous and disorganized, with excessively branched leaky vessels. This enhances vascular permeability, which in turn is associated with high interstitial fluid pressure, and a reduction in blood perfusion and oxygenation. Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time window. However, anti-angiogenics may also excessively prune tumor vessels in a dose and time-dependent manner, which induces hypoxia and immunosuppression, including increased expression of the immune checkpoint programmed death receptor ligand (PD-L1). This review focuses on revisiting the concept of anti-angiogenesis in combination with immunotherapy as a strategy for cancer treatment.
446 citations
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University of Geneva1, University of Helsinki2, Katholieke Universiteit Leuven3, University of Washington4, University of Wisconsin-Madison5, Heidelberg University6, German Cancer Research Center7, University of Nottingham8, VU University Amsterdam9, University of California, Irvine10, University of California, San Francisco11, French Institute of Health and Medical Research12, Harvard University13, Maine Medical Center14, University of Turin15, National Institutes of Health16, University of Texas Southwestern Medical Center17, University of Lausanne18, University of Missouri19, École Polytechnique Fédérale de Lausanne20, Uppsala University21, University of Arkansas for Medical Sciences22, University of Bern23, University of Virginia24, Imperial College London25, University of California, San Diego26, University College London27, Flanders Institute for Biotechnology28, University of Oxford29, University of California, Los Angeles30, University of Texas MD Anderson Cancer Center31, University of Toronto32, University of Illinois at Chicago33, University of Amsterdam34, George Washington University35, University of Liège36, University of Eastern Finland37, Ludwig Institute for Cancer Research38, Indiana University39, University of Edinburgh40, Maastricht University41, Loyola University Medical Center42, National Scientific and Technical Research Council43, University of Bari44, University of Fribourg45, Ohio State University46, University of Melbourne47, University of Antwerp48, University of Münster49
TL;DR: In vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis are described and critical aspects that are relevant for their execution and proper interpretation are highlighted.
Abstract: The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
397 citations