Prophylaxis of metastases formation by unspecific immunologic stimulation associated with heparintherapy

Kiricuţă, I; Todoruţiu, C; Muresian, Titus; Rişcă, R

doi:10.1002/1097-0142(197306)31:6<1392::aid-cncr2820310614>3.0.co;2-9

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…Our current findings are consistent with abundant in vitro and in vivo laboratory data, which suggest that anticoagulants, particularly LMWH, exert an antineoplastic effect 15–30, 50, 77. It has been reported that heparins inhibit primary tumor growth, reduce tumor cell motility, inhibit tumor cell migration, reduce the formation of metastases, enhance the antitumor effects of chemotherapy, and prolong the survival of laboratory animals after tumor cell inoculation 18, 24, 27, 31, 78–91.…”

Section: Discussionsupporting

confidence: 89%

“…Patients with cancer frequently have laboratory evidence of hemostatic activation,7–10 and patients who are diagnosed with an idiopathic venous thrombosis are at increased risk of subsequently developing cancer 11–14. Considerable experimental data indicate that anticoagulants, in particular low‐molecular‐weight heparin (LMWH) and unfractionated heparin (UFH), exert an antitumor effect 15–32…”

mentioning

confidence: 99%

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A meta‐analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment

Kuderer

Khorana

Lyman

et al. 2007

Cancer

196

100

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BACKGROUND. Preclinical evidence suggests that anticoagulants, in particular the low‐molecular‐weight heparins (LMWH), exert an antitumor effect, whereas clinical trials have reported conflicting results. The authors conducted a comprehensive, systematic review and meta‐analysis of the evidence from randomized controlled trials (RCTs), to evaluate the impact of anticoagulants on survival and safety in cancer patients without venous thromboembolism. METHODS. A comprehensive systematic literature review of RCTs was performed without language restrictions through May 2006 with subsequent updates to the end of 2006, including an exhaustive search of electronic databases, major conference proceedings, article references, and content experts. Two reviewers extracted data independently. Primary study outcomes were 1‐year overall mortality and all bleeding complications. Major and fatal bleeding complications were secondary outcomes. RESULTS. Across all 11 studies that were identified, anticoagulation significantly decreased 1‐year overall mortality with a relative risk (RR) of 0.905 (95% confidence interval [95% CI], 0.847–0.967; P = .003). The RR for mortality was 0.877 (95% CI, 0.789–0.975; P = .015) for LMWH, compared with an RR of 0.942 (95% CI, 0.854–1.040; P = .239) for warfarin, resulting in an absolute risk difference (ARD) of 8% for LMWH and an ARD of 3% for warfarin. Improved survival with anticoagulation may be dependent on tumor type. Major bleeding episodes occurred less frequently in patients who received LMWH (ARD, 1%) compared with patients who received warfarin (ARD, 11.5%; P < .0001). Overall, fatal bleeding occurred rarely (ARD, 0.32%; P = .542). CONCLUSIONS. Anticoagulants, particularly LMWH, significantly improved overall survival in cancer patients without venous thrombosis while increasing the risk for bleeding complications. However, given the limitations of available data, the use of anticoagulants as antineoplastic therapy cannot be recommended until additional RCTs confirm these results. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

A meta‐analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment

Kuderer

Khorana

Lyman

et al. 2007

Cancer

196

100

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“…Heparin has been known for some years to have antitumor effects, 80 ascribed to nonspecific immune stimulation as well as the anticoagulant effect. 8081 Inhibition of thrombin may play a role, since this enzyme has mul-tiple biological effects, 82 although this has not always decreased metastasis in experimental models.…”

Section: Heparinmentioning

confidence: 99%

Hemostasis and Malignancy

Francis¹,

Biggerstaff²,

Amirkhosravi³

1998

Semin Thromb Hemost

123

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There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

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“…Prophylactic effects of BCG based on nonspecific stimulation of tumor defense have often been described [2,4,9,11]. Using i.v.…”

Section: Discussionmentioning

confidence: 99%

Increased incidence of lung metastases of sarcoma 276 bearing XVII/Berlin mice after total body irradiation and BCG

Arnold¹,

Graffi²

1983

Clin Exp Metast

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Prophylaxis of metastases formation by unspecific immunologic stimulation associated with heparintherapy

Cited by 16 publications

References 11 publications

A meta‐analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment

A meta‐analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment

Hemostasis and Malignancy

Increased incidence of lung metastases of sarcoma 276 bearing XVII/Berlin mice after total body irradiation and BCG

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