The History of Armand Trousseau and Cancer-Associated Thrombosis

Metharom, Pat; Falasca, Marco; Berndt, Michael C.

doi:10.3390/cancers11020158

Cited by 40 publications

(24 citation statements)

References 18 publications

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“…After the report for a higher incidence of the clot formation in cancer patients from the French physician, Armand Trousseau, in 1865, people began to realize that thrombosis, tumor growth, and metastasis are always associated with the abnormal blood coagulation. Thrombin, which is a member of the chymotrypsin family, plays an important role in blood coagulation cascades. , Therefore, thrombin is a worth-studying molecule, which is vital for the development of the treatment of cancer. − …”

Section: Introductionmentioning

confidence: 99%

Light Chain Mutation Effects on the Dynamics of Thrombin

Xiao

Salsbury

2021

J. Chem. Inf. Model.

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Thrombin plays an important role in the process of hemostasis and blood coagulation. Studies in thrombin can help us find ways to treat cancer because thrombin is able to reduce the characteristic hypercoagulability of cancer. Thrombin is composed of two chains, the light chain and the heavy chain. The function of the heavy chain has been largely explored, while the function of the light chain was obscured until several disease-associated mutations in the light chain come to light. In this study, we want to explore the dynamic and conformation effects of mutations on the light chain further to determine possible associations between mutation, conformational changes, and disease. The study, which is a follow-up for our studies on apo thrombin and the mutant, ΔK9, mainly focuses on the mutants E8K and R4A. E8K is a diseaseassociated mutation, and R4A is used to study the role of Arg4, which is suggested experimentally to play a critical role for thrombin's catalytic activities. We performed five all-atom one microsecond-scale molecular dynamics (MD) simulations for both E8K and R4A, and quantified the changes in the conformational ensemble of the mutants. From the root-mean-square fluctuations (RMSF) for the α-carbons, we find that the atomic fluctuations change in the mutants in the 60s loop and γ loop. The correlation coefficients for the α-carbons indicate that the correlation relation for atom-pairs in the protein is also impacted. The clustering analysis and the principal component analysis (PCA) consistently tell us that the catalytic pocket and the regulatory loops are destabilized by the mutations. We also find that there are two binding modes for Na + by clustering the vector difference between the Na + ions and the 220s loop. After further analysis, we find that there is a relation between the Na + binding and the rigidification of the γ loop, which may shed light on the mysterious role of the γ loop in thrombin.

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Section: Introductionmentioning

confidence: 99%

Light Chain Mutation Effects on the Dynamics of Thrombin

Xiao

Salsbury

2021

J. Chem. Inf. Model.

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“…Indeed, there is a significantly increased risk of thromboembolism in cancer patients as compared to the general population [1,2]. This correlation, independently noted by Dr. Jean-Baptiste Bouillaud and Dr. Armand Trousseau in the 19th century, has been well reported [3,4]. Clinical risk factors for thrombotic complications include a wide range of factors such as patient-related, cancer-related and treatment-related risk factors [5,6].…”

Section: Introductionmentioning

confidence: 90%

Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis

Almeida

Rondon

Gomes

et al. 2019

Cells

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The establishment of prothrombotic states during cancer progression is well reported but the precise mechanisms underlying this process remain elusive. A number of studies have implicated the presence of the clotting initiator protein, tissue factor (TF), in circulating tumor-derived extracellular vesicles (EVs) with thrombotic manifestations in certain cancer types. Tumor cells, as well as tumor-derived EVs, may activate and promote platelet aggregation by TF-dependent and independent pathways. Cancer cells and their secreted EVs may also facilitate the formation of neutrophil extracellular traps (NETs), which may contribute to thrombus development. Alternatively, the presence of polyphosphate (polyP) in tumor-derived EVs may promote thrombosis through a TF-independent route. We conclude that the contribution of EVs to cancer coagulopathy is quite complex, in which one or more mechanisms may take place in a certain cancer type. In this context, strategies that could attenuate the crosstalk between the proposed pro-hemostatic routes could potentially reduce cancer-associated thrombosis.

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“…156 years ago, Armand Trousseau documented that venous thromboembolism (VTE) “phlegmatia alba dolens” is frequently associated with malignant tumors ( 21 , 22 ). VTE is always associated with platelet activation.…”

Section: Platelet-tumor Cell Interaction During the Metastatic Cascadmentioning

confidence: 99%

The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors

2021

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Mammalian platelets, devoid of nuclei, are the smallest cells in the blood stream. They are essential for hemostasis, but also transmit cell signals that are necessary for regenerative and generative processes such as inflammation, immunity and tissue repair. In particular, in malignancies they are also associated with cell proliferation, angiogenesis, and epithelial-mesenchymal transition. Platelets promote metastasis and resistance to anti-tumor treatment. However, fundamental principles of the interaction between them and target cells within tumors are complex and still quite obscure. When injected into animals or circulating in the blood of cancer patients, cancer cells ligate platelets in a timely manner closely related to platelet activation either by direct contact or by cell-derived substances or microvesicles. In this context, a large number of different surface molecules and transduction mechanisms have been identified, although the results are sometimes species-specific and not always valid to humans. In this mini-review, we briefly summarize the current knowledge on the role of the direct and indirect platelet-tumor interaction for single steps of the metastatic cascade and specifically focus on the functional role of P-selectin.

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The History of Armand Trousseau and Cancer-Associated Thrombosis

Abstract: “Je suis perdu; une phlegmatia qui vient de se déclarer cette nuit, ne me laisse aucun doute sur nature de mon mal [...]

Cited by 40 publications

References 18 publications

Light Chain Mutation Effects on the Dynamics of Thrombin

Light Chain Mutation Effects on the Dynamics of Thrombin

Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis

The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors

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