Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncogenic upregulation of tissue factor (TF) and release of TF-containing microvesicles play an important role in cancer-related coagulopathy (Trousseau's syndrome), angiogenesis, and disease progression. In addition, certain types of host cells (stromal cells, inflammatory cells, activated endothelium) may also express TF. Although the relative contribution of host-related versus tumor-related TF to tumor progression is not known, our recent studies indicate that the role of both sources of TF in tumor formation is complex and context-dependent. Disruption of TF expression/activity in cancer cells leads to tumor growth inhibition in immunodeficient mice, even in cases where TF overexpression is driven by potent oncogenes ( K-RAS or EGFR). Interestingly, TF expression in vivo appears to be influenced by many factors, including the level of oncogenic transformation, tumor microenvironment, and differentiation from cancer stem-like cells. We postulate that activation of TF signaling and coagulation may deliver growth-promoting stimuli (e.g., fibrin, thrombin, platelets) to dormant cancer stem cells (CSCs). Functionally, these influences may be tantamount to formation of a provisional (TF-dependent) cancer stem cell niche. As such, these changes may contribute to the involvement of CSCs in tumor growth, angiogenesis, and metastasis.
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PMID:Diverse roles of tissue factor-expressing cell subsets in tumor progression. 1864 22

Cancer is characterized by bidirectional interrelations between tumour progression, coagulation activation, and inflammation. Tissue factor (TF), the principal initiator of the coagulation protease cascade, is centrally positioned in this complex triangular network due to its pleiotropic effects in haemostasis, angiogenesis, and haematogenous metastasis. While formation of macroscopic thrombi is the correlate of cancer-associated venous thromboembolism (VTE), a major healthcare burden in clinical haematology and oncology, microvascular thrombosis appears to be critically important to blood-borne tumour cell dissemination. In this regard, expression of TF in malignant tissues as well as shedding of TF-bearing microparticles into the circulation are thought to be regulated by defined genetic events relevant to pathological cancer progression, thus directly linking Trousseau's syndrome to molecular tumourigenesis. Because pharmacological inhibition of the TF pathway in selective tumour types and patient subgroups would be in line with the modern concept of individualized, targeted anti-cancer therapy, this review will focus on the role of TF in tumour biology and cancer-associated VTE.
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PMID:Crosstalk between cancer and haemostasis. Implications for cancer biology and cancer-associated thrombosis with focus on tissue factor. 2179 69

Clinically relevant clotting abnormalities in cancer patients are referred to as Trousseau's syndrome. While thrombotic complications such as venous thromboembolism are most frequent in every day's practice, cancer patients may also experience severe bleeding symptoms due to complex systemic coagulopathies, including disseminated intravascular coagulation, haemolytic thrombotic microangiopathy, and hyperfibrinolysis. The pathophysiology of Trousseau's syndrome involves all aspects of Virchow's triad, but previous basic research has mainly focused on the cellular and molecular mechanisms underlying blood hypercoagulability in solid cancers and haematological malignancies. In this regard, over-expression of tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, by primary tumour cells and increased shedding of TF-bearing plasma microparticles are critical to both thrombus formation and cancer progression. However, novel findings on intrinsic contact activation in vivo, such as the release of polyphosphates or DNA by activated platelets and neutrophils, respectively, have pointed to additional pathways in the complex pathophysiology of Trousseau's syndrome.
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PMID:Pathophysiology of Trousseau's syndrome. 2540 91

Thrombosis is a major cause of morbidity and mortality in cancer patients. The pathogenesis of blood coagulation activation in oncological patients is complex and involves both clinical and biological factors. Abnormalities in one or more coagulation test are common in cancer patients, even without thrombotic manifestations, indicating an ongoing hypercoagulable condition. Moreover, venous thromboembolism (VTE) can be the first symptom of an occult malignancy in an otherwise healthy individual. The levels of laboratory markers of activation of blood coagulation parallel the development of malignancy, being the coagulant mechanisms important for both thrombogenesis and tumor progression. Besides general clinical risk factors for VTE, also disease-specific clinical factors, i.e., type and stage of the tumor, and anticancer therapies increase the thrombotic risk in these patients. Furthermore, biological factors, including the cancer cell-specific prothrombotic properties together with the host cell inflammatory response to the tumor, are relevant as well as unique players in the pathogenesis of the cancer-associated hypercoagulability. Cancer cells produce and release procoagulant and fibrinolytic proteins, inflammatory cytokines, and procoagulant microparticles. They also express adhesion molecules binding to the receptors of host vascular cells (i.e., endothelial cells, platelets, and leukocytes), thereby stimulating the prothrombotic properties of these normal cells, including the shed of cell-specific microparticles and neutrophil extracellular traps. Of interest, several genes responsible for the cellular neoplastic transformation drive the programs of hemostatic properties expressed by cancer tissues. A better understanding of such mechanisms will help the development of novel strategies to prevent and treat the Trousseau's syndrome (i.e., cancer-associated thrombosis).
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PMID:Pathophysiology 1. Mechanisms of Thrombosis in Cancer Patients. 3131 78

A 51-year-old woman who presented with a large cystic liver tumor with mural nodules in the lateral segment developed Trousseau's syndrome. A mural nodule directly invaded her liver parenchyma. Metastatic nodules were detected in the right lobe and portal/paraaortic lymph nodes. The pathological findings showed mucin-producing adenocarcinoma cells to have invaded the fibrous stroma forming a micropapillary cluster. She developed obstructive jaundice due to tumor progression and subsequently died of hepatic failure. Invasive biliary mucinous cystic neoplasm (MCN) is a rare form of a malignant tumor with a relatively favorable prognosis. This is a very rare case biliary MCN with invasive carcinoma that showed intrahepatic and lymph node metastases.
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PMID:A Biliary Mucinous Cystic Neoplasm with Intrahepatic and Lymph Node Metastases. 3271 14