Hemostatic Mechanisms and Metastasis

1. Is there Clinical Relevance for Therapies which Disrupt the Metastatic Cascade?.- I. Introduction.- II. Primary Cancer and Vascular Invasion.- A. Tumor Stage.- B. Histology and Differentiation.- C. Tissue of Origin.- III. Circulating Cancer Cells.... Read more

1. Is there Clinical Relevance for Therapies which Disrupt the Metastatic Cascade?.- I. Introduction.- II. Primary Cancer and Vascular Invasion.- A. Tumor Stage.- B. Histology and Differentiation.- C. Tissue of Origin.- III. Circulating Cancer Cells.- IV. Metastatic Potential of Metastases.- V. Summary.- 2. Overview of the Metastatic Cascade.- I. Is Metastasis a Random or Non-Random Process?.- A. Heterogeneity.- B. Clones.- C. Randomness or Non-Randomness.- D. Conclusions.- II. Release 1.- A. Site.- B. Detachment Factors.- 1. Growth-rate and detachment.- 2. Necrosis and detachment.- 3. Enzymes and detachment.- III. Invasion.- IV. Arrest.- A. Biophysical Aspects of Arrest.- B. The Role of Platelets and Fibrin in Arrest.- C. General Host Effects.- D. Repetitive Events.- V. Release 2.- VI. The Formation of Metastases from Micrometastases.- VII. Conclusions.- 3. Overview on Blood Coagulation Proteins.- I. Introduction.- II. Structural Characteristics of Serine Proteinases.- III. The Role of Vitamin K.- IV. Fibrinogen.- V. Regulation of Blood Coagulation.- A. The Intrinsic Pathway.- B. The Extrinsic Pathway.- C. The Relationship between the Intrinsic and Extrinsic Pathways.- VI. Inhibitors of Blood Coagulation.- VII. Role of Platelets in Blood Coagulation.- VIII. Fibrinolysis.- 4. The Microinjury Hypothesis and Metastasis.- I. The Silent Sector of the Metastatic Cascade.- II. The Microinjury Hypothesis.- III. Conclusion.- 5. Hemostatic Abnormalities in Tumor-Bearing Animals.- I. Introduction.- II. Animal Models of Dissemination.- III. Lung Colony Models.- IV. Spontaneous Metastasis Models.- V. Pathophysiological Mechanisms.- VI. Conclusions.- 6. Evidence for a Tumor Proteinase in Blood Coagulation.- I. Introduction.- II. Purification of Cancer Procoagulant.- III. Characterization of Cancer Procoagulant.- IV. Distribution of Cancer Procoagulant.- V. Tissue Factor as the Tumor Procoagulant.- VI. Rationale For Cancer Procoagulant.- 7. Relationship between Procoagulant Activity and Metastatic Capacity of Tumor Cells.- I. Introduction.- II. Fibrin and Tumors.- III. Cancer Cell Procoagulants.- IV. Role of Procoagulants in Metastasis.- A. Hematologic Phase Model.- B. Spontaneous Models.- V. Clinical Relevance.- 8. Fibrin Formation: Implications for Tumor Growth and Metastasis.- I. Introduction and Historical Background.- II. The Nature of Fibrin Deposits in Tissues.- III. Fibrin is a Component of the Tumor Microenvironment.- A. Guinea Pig Hepato (bile duct) Carcinomas.- 1. Line 1 carcinomas.- 2. Line 10 carcinomas.- B. Mouse Breast Carcinomas.- C. Human Tumors.- 1. Infiltrating ductal breast carcinoma.- 2. Hodgkin''s disease and other malignant lymphomas.- D. Conclusions.- IV. Tumor Secreted Mediators can Generate Tumor Associated Fibrin Deposits.- A. Tumor Secreted Vascular Permeability Factor (PF).- B. Tumor Associated Procoagulants.- 1. Tissue factor-like activity.- 2. Factor X cleaving activities.- 3. Shed plasma membrane vesicles.- 4. Thrombin-like and factor XIII-like activities.- V. Summary and Conclusions.- 9. Perspectives on the Role of Platelets in Hemostasis and Thrombosis.- I. Introduction.- A. Platelet Adhesion.- B. Platelet Release Reaction.- C. Platelet Aggregation.- D. Coagulant Activities of Platelets.- E. Role of Platelets in Contact Activation.- II. Interaction of Platelets with Coagulation Factors.- A. Interactions of Platelets with Factor VIII.- B. The Interaction of Platelets with Factor V.- C. Interactions of Platelets with Vitamin K-Dependent Clotting Factors.- D. The Role of Platelets in the Intrinsic Activation of Factor X and Prothrombin.- E. Platelet Activation as It Relates to the Conversion of Prothrombin to Thrombin.- III. Other Potential Consequences Of Platelet Activation.- 10. Mechanisms of Platelet Aggregation by Murine Tumor Cell Spheroids.- I. Introduction.- II. Experimental Systems.- III. Platelet-Vesicle Interactions.- A. Platelet Aggregating Activity Shed Spontaneously by Cells.- 1. Spontaneous shedding of vesicles by 15091A.- 2. Activity of vesicles isolated by sucrose density gradient centrifugation.- B. Platelet Aggregating Activity Released by Augmented Shedding.- 1. Isotonic low ionic strength medium.- 2. Urea.- 3. Trypsin.- IV. Conclusions.- 11. Heterogenous Mechanisms of Tumor Cell-Induced Platelet Aggregation with Possible Pharmacological Strategy Toward Prevention of Metastases.- I. Introduction.- II. Materials and Methods.- III. Results.- A. Tumors which Require Complement, a Vesicular Cell Surface, Sialo-Lipoprotein Component, Divalent Cation and a Stable Plasma Factor for Platelet Aggregation Activity.- B. Tumors which Aggregate Platelets via the Generation of Thrombin.- C. Tumors which Require a Trypsin Sensitive Protein for Platelet Aggregating Activity.- D. Effect of Pharmacologic Agents on the Three Mechanisms of Tumor-Induced Platelet Aggregation.- IV. Discussion.- 12. Tumor Cysteine Proteinases, Platelet Aggregation and Metastasis.- I. Cysteine Proteinases.- II. Less