Abstract:
:The quiescent vascular system in the adult body represents the imbalanced net outcome of overproduction of endogenous angiogenesis inhibitors and reduced levels of angiogenic factors. While some endogenous inhibitors are expressed under physiological conditions, they can also be generated in association with tumor growth. Angiostatin is such a specific angiogenesis inhibitor produced by tumors. It inhibits primary and metastatic tumor growth by blocking tumor angiogenesis. Having demonstrated potent antitumor activity in animal studies, angiostatin is now in clinical trials for human cancer therapy. Angiostatin is not a novel protein molecule coded by novel DNA sequences. Instead, it is an internal proteolytic fragment of a known protein, plasminogen. Surprisingly, most kringle domains of plasminogen only inhibit angiogenesis when cleaved as fragments from their parent protein that lacks antiangiogenic activity. These findings suggest that they are cryptic fragments hidden in large protein molecules. Thus, proteolytic processing plays a critical role in down-regulation of angiogenesis. Despite proteolytic processing, the antiangiogenic mechanism of angiostatin remains an enigma. Without knowing the mechanisms, it is difficult to predict the ultimate outcome of ongoing clinical trials. In this article, we discuss what is known about angiostatin and how this molecule specifically inhibits angiogenesis. We hope that the information will be useful for further development of angiostatin and its related inhibitors as therapeutic agents.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Cao Y,Xue Ldoi
10.1055/s-2004-822973subject
Has Abstractpub_date
2004-02-01 00:00:00pages
83-93issue
1eissn
0094-6176issn
1098-9064journal_volume
30pub_type
杂志文章,评审abstract::Systolic heart failure is a common syndrome whose incidence is expected to increase. Several treatment modalities, such as beta-blockers and angiotensin-converting enzyme inhibitors, improve survival. Whether antithrombotic treatment is effective remains to be elucidated, although observations suggest a prothrombotic ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1234145
更新日期:2009-07-01 00:00:00
abstract::In order to assess inhibitor development in previously untreated patients (PUPs) with severe (factor VIII [FVIII]<1%) and moderate (FVIII 1 to 5%) hemophilia A, a prospective study was initiated in 1976. During the 23-year study period, 72 hemophiliacs were frequently exposed prophylactically or on demand to plasma-de...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2002-32664
更新日期:2002-06-01 00:00:00
abstract::Current guidelines for venous thromboembolism (VTE) primary prophylaxis are based on randomized clinical trials that exclude subjects at a potentially high bleeding risk. Thus no specific recommendation/algorithm for pharmacological prophylaxis in patients with thrombocytopenia and/or platelet dysfunction is available...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1273090
更新日期:2011-04-01 00:00:00
abstract::The two components of biological variability are interindividual variability, which is the variability due to the heterogeneity of physiologic influences among subjects, and intraindividual variability, which is due to the variability in the same individual over time. Analysis of biological variation is crucial for es...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0029-1214155
更新日期:2009-02-01 00:00:00
abstract::Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in thi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1666823
更新日期:2018-09-01 00:00:00
abstract::The long-term success rate of coronary angioplasty is only 50 to 70% due to restenosis. The pathophysiologic mechanism of this event is mainly mediated by smooth muscle cell proliferation. To some extent, it can be inhibited by heparin. The introduction of LMWHs allows for prophylaxis against restenosis on an outpatie...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Arterial and venous thromboses are sustained by development of intraluminal thrombi, respectively, within the venous and arterial systems. The composition and structure of arterial and venous thrombi have been historically considered as being very different. Arterial thrombi (conventionally defined as "white") have be...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1607202
更新日期:2018-04-01 00:00:00
abstract::Platelet-lowering therapy in myeloproliferative disorders includes cytostatic drugs, mainly hydroxyurea, interferon alpha, and anagrelide. Anagrelide is the latest addition to the therapeutic arsenal, and the basis for its use is reviewed. The platelet-lowering efficacy is 70 to 80% in essential thrombocythemia, and t...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-939437
更新日期:2006-04-01 00:00:00
abstract::Treatment of patients with inhibitors to FVIII remains a complex clinical problem. Although characterizing the individual patient may aid in the initial development of a care plan, no treatment is uniformly reliable for all patients. Experts in the field are as likely to disagree as agree when it comes to choosing tre...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994002
更新日期:1993-01-01 00:00:00
abstract::Anti-factor Xa methods have been generally accepted for the monitoring of heparin treatment mainly due to their sensitivity to LMWH and excellent performance on automated equipment. When such equipment is not available, as in small laboratories or on the night shift, there is a need for a simple manual method. In the ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::We have explored the molecular basis of the clinical therapeutic effect of factor VIIa in hemophilia A using empirical reconstituted in vitro thrombin generation models. Tissue factor acts as a receptor and activator of preexistent but virtually inactive two-chain plasma factor VIIa. However, most of the factor VII ci...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-8454
更新日期:2000-01-01 00:00:00
abstract::Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-985754
更新日期:2007-09-01 00:00:00
abstract::Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1598062
更新日期:2017-06-01 00:00:00
abstract::Patients receiving heparin are at risk of developing heparin-induced thrombocytopenia (HIT). Whereas in HIT I only reversible mild thrombocytopenia occurs within the first days of heparin treatment, HIT II may lead to potentially life-threatening thromboembolic events. Pediatric patients suffering from HIT II have bee...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2002-35285
更新日期:2002-10-01 00:00:00
abstract::Plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis, is induced in thrombotic, fibrotic, and cardiovascular diseases, which in turn primarily afflict the older population. This induction of PAI-1 may play an important role in the pathology of these diseases as PAI-1 can regulate the dissol...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1384635
更新日期:2014-09-01 00:00:00
abstract::Clinical and laboratory data of children with von Willebrand disease (VWD) types have been derived from retrospective studies and small case series. This article reports on the clinical and laboratory data of a large pediatric cohort in one single Argentinian center. The biological and clinical responses to desmopress...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0031-1281043
更新日期:2011-07-01 00:00:00
abstract::Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and hi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1055/s-2007-1002654
更新日期:1991-10-01 00:00:00
abstract::In the pathogenesis of vascular disease, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Tissue factor (T...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-933338
更新日期:2006-02-01 00:00:00
abstract::Patients with end-stage renal disease suffer from complex hemostatic disorders. Uremic patients show a bleeding diathesis that is mainly due to abnormalities of primary hemostasis; in particular, platelet dysfunction and impaired platelet-vessel wall interaction. However, despite decreased platelet function, these pat...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-835678
更新日期:2004-10-01 00:00:00
abstract::Several studies have suggested that patients with non-O blood group have an increased risk of both venous and arterial thromboembolic events. On the contrary, the role of ABO blood group on the risk of bleeding complications remains unclear. Thus, we performed a meta-analysis of the literature with the aim of assessin...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,meta分析,评审
doi:10.1055/s-0032-1329550
更新日期:2013-02-01 00:00:00
abstract::Fibrin formed from fibrinogen is the main component of thrombi. Clot structure is characterized by fiber thickness and pore size, which differs within a given clot and between individuals. Plasma clot architecture is largely determined by the quantity and quality of fibrinogen. Plasma fibrinogen concentrations are mos...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1579636
更新日期:2016-06-01 00:00:00
abstract::We present three clinical cases that illustrate some of the key features of the diagnosis and management of immune-mediated heparin-induced thrombocytopenia (HIT). The importance of having a high clinical suspicion for HIT in the appropriate clinical setting is emphasized. Early therapeutic decisions should be based o...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2004-831040
更新日期:2004-06-01 00:00:00
abstract::Pulmonary embolism (PE) has long been described in children. Nevertheless, most of the algorithms applied to patients within this age range, from diagnosis to therapy, have been adapted from adult protocols. This article reviews the progresses that occurred to PE in children placing them in historical perspective with...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1297168
更新日期:2011-10-01 00:00:00
abstract::Hemophilia A and B gene therapy requires long-term and stable expression of coagulation factor VIII (FVIII) or factor IX (FIX), respectively, and would need to compare favorably with protein replacement therapy. Onco-retroviral and lentiviral vectors are attractive vectors for gene therapy of hemophilia. These vectors...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-825632
更新日期:2004-04-01 00:00:00
abstract::Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombo...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1001886
更新日期:1994-01-01 00:00:00
abstract::Rheological alterations are commonly found in malignant disease and are most pronounced in advanced-stage cancer. Although most of these changes are caused by cancer-unspecific mechanisms, it has been shown that the extent of these changes in some cancer types is related with the stage of cancer, prognosis of disease,...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-44641
更新日期:2003-10-01 00:00:00
abstract::Hip replacement surgery carries a high risk of thromboembolic complications, and pharmacological prophylaxis is routinely adopted in clinical practice. Meta-analyses have indicated that low molecular weight heparins (LMWHs) are clinically superior to conventional prophylaxis with unfractionated heparin. These analyses...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Cancer often leads to the activation of coagulation, manifesting as disseminated intravascular coagulation (DIC) in its most extreme form. DIC is characterized by systemic intravascular coagulation activation (leading to deposition of intravascular platelets and fibrin) and simultaneous consumption of coagulation prot...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-1687890
更新日期:2019-06-01 00:00:00
abstract::Severe acute inflammation in chronic inflammatory bowel disease is associated with large wound areas and ulcerations that show spontaneous hemorrhage or marked friability. Therefore, an enormous potential of hemostasis and wound healing is required. Coagulation studies demonstrate a deficiency of factor XIII that is i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-999045
更新日期:1996-01-01 00:00:00
abstract::The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemo...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00