REVIEWS — Tumour micrometastases: the influence of angiogenesis

Introduction: Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis—the development of an independent blood supply—is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. Methods: This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. Conclusions: Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

[1]  F. Shanahan,et al.  Micrometastases in esophagogastric cancer: high detection rate in resected rib segments. , 1999, Gastroenterology.

[2]  G. Lyman,et al.  Molecular staging of malignant melanoma: correlation with clinical outcome. , 1998, JAMA.

[3]  H. Redmond,et al.  Significance of angiogenesis in cancer therapy , 1998, The British journal of surgery.

[4]  C. V. D. van de Velde,et al.  Micrometastases and survival in stage II colorectal cancer. , 1998, The New England journal of medicine.

[5]  N. Nelson Inhibitors of angiogenesis enter phase III testing. , 1998, Journal of the National Cancer Institute.

[6]  T. Yeatman,et al.  Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. , 1998, Annals of surgery.

[7]  Thomas Boehm,et al.  Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance , 1997, Nature.

[8]  R. Kerbel A cancer therapy resistant to resistance , 1997, Nature.

[9]  Mihaela Skobe,et al.  Halting angiogenesis suppresses carcinoma cell invasion , 1997, Nature Medicine.

[10]  M. Fan,et al.  Lymph node micrometastases from breast carcinoma , 1997, Cancer.

[11]  S. Fox,et al.  Association of tumor angiogenesis with bone marrow micrometastases in breast cancer patients. , 1997, Journal of the National Cancer Institute.

[12]  A. Mantovani,et al.  Molecular mechanisms of blood vessel formation. , 1997, Trends in biochemical sciences.

[13]  T. Reimer,et al.  Immunohistochemically Detected Lymph‐Node Micrometastases in Breast Cancer and their Correlation with Prognostic Factors , 1997 .

[14]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[15]  J M Pluda,et al.  Tumor-associated angiogenesis: mechanisms, clinical implications, and therapeutic strategies. , 1997, Seminars in oncology.

[16]  K. Dameron,et al.  Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity , 1997, Oncogene.

[17]  William Arbuthnot Sir Lane,et al.  Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth , 1997, Cell.

[18]  J. Folkman,et al.  Blood Vessel Formation: What Is Its Molecular Basis? , 1996, Cell.

[19]  R. Weichselbaum,et al.  Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer. , 1996, Journal of the National Cancer Institute.

[20]  Y. Kakeji,et al.  TNP-470/minocycline/cytotoxic therapy: a systems approach to cancer therapy. , 1996, European journal of cancer.

[21]  A. Nicholson,et al.  Angiogenesis in primary lung cancer and lung secondaries. , 1996, European journal of cancer.

[22]  P. Polverini How the extracellular matrix and macrophages contribute to angiogenesis-dependent diseases. , 1996, European journal of cancer.

[23]  R. Hynes,et al.  Tumour suppressor genes and angiogenesis: the role of TP53 in fibroblasts. , 1996, European journal of cancer.

[24]  S. Braun,et al.  Re: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. , 1996, Journal of the National Cancer Institute.

[25]  L. Ellis,et al.  Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  K. Pantel,et al.  Immunocytochemical detection of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma. , 1996, Journal of the National Cancer Institute.

[27]  K. Pantel,et al.  Immunocytochemical detection of isolated epithelial tumor cells in bone marrow of patients with pancreatic carcinoma. , 1996, American journal of surgery.

[28]  L. Hakansson,et al.  Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes' B colorectal carcinoma: an immunohistochemical study. , 1996, The European journal of surgery = Acta chirurgica.

[29]  J. Folkman,et al.  Angiostatin induces and sustains dormancy of human primary tumors in mice , 1996, Nature Medicine.

[30]  J. Rosai,et al.  Polymerase chain reaction in the detection of micrometastases and circulating tumor cells , 1996, Cancer.

[31]  A. Giuliano Guest editorial: Sentinel lymphadenectomy in primary breast carcinoma: An alternative to routine axillary dissection , 1996, Journal of surgical oncology.

[32]  R. Gamelli,et al.  Thrombospondin 1 synthesis and function in wound repair. , 1996, The American journal of pathology.

[33]  N. Bouck P53 and angiogenesis. , 1996, Biochimica et biophysica acta.

[34]  F. Schildberg,et al.  Comparative analyses of bone marrow micrometastases in breast and gastric cancer , 1996, International journal of cancer.

[35]  M. Shipp,et al.  Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. , 1996, Cancer research.

[36]  S. Noguchi,et al.  Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification. , 1996, The American journal of pathology.

[37]  J. Folkman Tumor angiogenesis and tissue factor , 1996, Nature Medicine.

[38]  David E. Housman,et al.  Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours , 1996, Nature.

[39]  M. Cummings,et al.  Occult axillary node metastases in breast cancer: their detection and prognostic significance. , 1996, British Journal of Cancer.

[40]  Y. Maehara,et al.  Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancer. , 1996, British Journal of Cancer.

[41]  R. Giavazzi,et al.  Matrix metalloproteinase inhibition: a review of anti-tumour activity. , 1995, Annals of oncology : official journal of the European Society for Medical Oncology.

[42]  D. Carney,et al.  Prognostic significance of microvessel density in lymph node negative breast carcinoma. , 1995, Human pathology.

[43]  F. Sarkar,et al.  Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. , 1995, The Journal of clinical investigation.

[44]  Clive R. Taylor,et al.  Detection of occult bone marrow micrometastases in patients with operable lung carcinoma. , 1995 .

[45]  L. Ellis,et al.  Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. , 1995, Cancer research.

[46]  A. Harris,et al.  Microvessel count predicts metastatic disease and survival in non‐small cell lung cancer , 1995, The Journal of pathology.

[47]  A. Giuliano,et al.  Improved Axillary Staging of Breast Cancer with Sentinel Lymphadenectomy , 1995, Annals of surgery.

[48]  P. Bornstein,et al.  Diversity of Function Is Inherent in Matricellular Proteins: an Appraisal of Thrombospondin I , 1995 .

[49]  Y. Chung,et al.  Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma. , 1995, British Journal of Cancer.

[50]  H. Redmond,et al.  Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model , 1995, The British journal of surgery.

[51]  B. Hoffman,et al.  Molecular controls of growth arrest and apoptosis: p53-dependent and independent pathways. , 1995, Oncogene.

[52]  S. Steinberg,et al.  Tumor angiogenesis in advanced stage ovarian carcinoma. , 1995, The American journal of pathology.

[53]  M. Goldberg,et al.  Transcriptional Regulation of the Rat Vascular Endothelial Growth Factor Gene by Hypoxia (*) , 1995, The Journal of Biological Chemistry.

[54]  K. Mimori,et al.  Overexpression of matrix metalloproteinase‐7 mRNA in human colon carcinomas , 1995, Cancer.

[55]  T. Fan,et al.  Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy. , 1995, Trends in pharmacological sciences.

[56]  D. Cheresh,et al.  Integrin α v β 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels , 1994, Cell.

[57]  D. Reintgen,et al.  Detection of Submicroscopic Lymph Node Metastases with Polymerase Chain Reaction in Patients with Malignant Melanoma , 1994, Annals of surgery.

[58]  K. Plate,et al.  Vascular endothelial growth factor and glioma angiogenesis: Coordinate induction of VEGF receptors, distribution of VEGF protein and possible In vivo regulatory mechanisms , 1994, International journal of cancer.

[59]  V. Rangnekar,et al.  Identification of bone marrow micrometastases in patients with prostate cancer , 1994, Cancer.

[60]  K. Satoh,et al.  Infrequent stromal expression of gelatinase A and intact basement membrane in intraductal neoplasms of the pancreas. , 1994, Gastroenterology.

[61]  L. Ellis,et al.  The implications of angiogenesis for the biology and therapy of cancer metastasis , 1994, Cell.

[62]  Lars Holmgren,et al.  Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma , 1994, Cell.

[63]  A. Harris,et al.  Cytokine networks in solid human tumors: regulation of angiogenesis , 1994, Journal of leukocyte biology.

[64]  K. Dameron,et al.  Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. , 1994, Science.

[65]  Shinzaburo Noguchi,et al.  The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase‐polymerase chain reaction , 1994, Cancer.

[66]  R. Kerbel,et al.  Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant melanomas. , 1994, The American journal of pathology.

[67]  Alice Chung,et al.  Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer , 1994, Annals of surgery.

[68]  Osborne Mp,et al.  Detection and management of bone marrow micrometastases in breast cancer. , 1994 .

[69]  D. Butler CNRS committee 'to break silence' on ethics , 1994, Nature.

[70]  Mark D. Johnson,et al.  Inhibition of angiogenesis by tissue inhibitor of metalloproteinase , 1994, Journal of cellular physiology.

[71]  W. Zhou,et al.  A fumagillin derivative angiogenesis inhibitor, AGM-1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogene expression in vascular endothelial cells. , 1994, Cancer research.

[72]  S. Shousha,et al.  Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction. , 1994, Cancer research.

[73]  A. Luini,et al.  Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features. , 1994, British Journal of Cancer.

[74]  D. Cheresh,et al.  Requirement of vascular integrin alpha v beta 3 for angiogenesis. , 1994, Science.

[75]  R. Poorman,et al.  Interstitial collagenase is required for angiogenesis in vitro. , 1994, Developmental biology.

[76]  Cord Sunderkötter,et al.  Macrophages and angiogenesis , 1994, Journal of leukocyte biology.

[77]  K. Smith-McCune,et al.  Demonstration and characterization of the angiogenic properties of cervical dysplasia. , 1994, Cancer research.

[78]  G. Evan,et al.  Oncogenes and cell death. , 1994, Current opinion in genetics & development.

[79]  M. Toner,et al.  The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma , 1994, The Journal of pathology.

[80]  L. Liotta,et al.  Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane. , 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[81]  S. Koscielny,et al.  Re: Local recurrences following mastectomy: support for the concept of tumor dormancy. , 1994, Journal of the National Cancer Institute.

[82]  E. Manseau,et al.  Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. , 1993, The American journal of pathology.

[83]  F. Burrows,et al.  Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[84]  David P. LeBrun,et al.  Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice , 1993, Cell.

[85]  A. Lee,et al.  Occult axillary lymph node metastases in "node-negative" breast carcinoma. , 1993, Human pathology.

[86]  W Blumenfeld,et al.  Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. , 1993, The American journal of pathology.

[87]  D. Liggitt,et al.  Systemic gene expression after intravenous DNA delivery into adult mice. , 1993, Science.

[88]  R. Crystal,et al.  In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. , 1993, Circulation research.

[89]  J. Tjandra,et al.  Detection and significance of occult metastases in node‐negative breast cancer , 1993, The British journal of surgery.

[90]  H. Adlercreutz,et al.  Genistein, a dietary-derived inhibitor of in vitro angiogenesis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[91]  F. Clayton,et al.  Pathologic correlates of prognosis in lymph node‐positive breast carcinomas , 1993, Cancer.

[92]  J. Denekamp,et al.  Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy , 1993 .

[93]  S. Braun,et al.  Micrometastatic tumour cells in bone marrow in colorectal cancer , 1993, The Lancet.

[94]  R. Pugh-Humphreys Macrophage-neoplastic cell interactions: implications for neoplastic cell growth. , 1992, FEMS microbiology immunology.

[95]  B. Teicher,et al.  Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. , 1992, Cancer research.

[96]  H. Seigler,et al.  Relationship between disease-free interval and survival in patients with recurrent melanoma. , 1992, Archives of surgery.

[97]  G. Bastert,et al.  Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  G. Schlimok,et al.  Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients , 1992, The Lancet.

[99]  D. Collins,et al.  Inhibition of angiogenesis by suramin. , 1992, Cancer research.

[100]  J. Coindre,et al.  Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. , 1992, British Journal of Cancer.

[101]  G. Nicolson,et al.  Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. , 1992, British Journal of Cancer.

[102]  M. Perricaudet,et al.  Adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin cDNA to human endothelial cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[103]  M. Brigden,et al.  'Macrophages' and their putative significance in human breast cancer. , 1992, British Journal of Cancer.

[104]  Gerard I. Evan,et al.  Induction of apoptosis in fibroblasts by c-myc protein , 1992, Cell.

[105]  D. Ingber,et al.  Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy. , 1992, Seminars in cancer biology.

[106]  D L Morton,et al.  Technical details of intraoperative lymphatic mapping for early stage melanoma. , 1992, Archives of surgery.

[107]  D. Ingber Extracellular matrix and cell shape: Potential control points for inhibition of angiogenesis , 1991, Journal of cellular biochemistry.

[108]  K. Pantel,et al.  Micrometastatic tumour cells in bone marrow of patients with gastric cancer: methodological aspects of detection and prognostic significance. , 1991, European journal of cancer.

[109]  V. Alves,et al.  Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins , 1991, Diseases of the colon and rectum.

[110]  M L Lesser,et al.  Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[111]  A. Giuliano,et al.  Occult metastases in the axillary lymph nodes of patients with breast cancer node negative by clinical and histologic examination and conventional histology. , 1991, Disease markers.

[112]  R. Cote,et al.  Sensitivity of immunocytochemical detection of breast cancer cells in human bone marrow. , 1991, Cancer research.

[113]  R. Gelber,et al.  Axillary node micrometastases and breast cancer , 1991, The Lancet.

[114]  L. Liotta,et al.  Augmentation of type IV collagenase, laminin receptor, and Ki67 proliferation antigen associated with human colon, gastric, and breast carcinoma progression. , 1991, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[115]  L. Liotta,et al.  Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation , 1991, Cell.

[116]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[117]  D. Ingber,et al.  Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth , 1990, Nature.

[118]  R. Schreiber,et al.  Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death , 1990, Nature.

[119]  I. Fidler,et al.  Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. , 1990, Cancer research.

[120]  G. Schlimok,et al.  Detection, characterization and tumorigenicity of disseminated tumor cells in human bone marrow. , 1990, Seminars in cancer biology.

[121]  J. Witte,et al.  Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[122]  J. Folkman What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[123]  Donald E. Ingber,et al.  How does extracellular matrix control capillary morphogenesis? , 1989, Cell.

[124]  D. Sedmak,et al.  Prognostic significance of cytokeratin-positive breast cancer metastases. , 1989, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[125]  H. Dvorak,et al.  Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. , 1989, Biochimica et biophysica acta.

[126]  A. Srivastava,et al.  The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0 mm thick) skin melanoma. A quantitative histologic study. , 1988, The American journal of pathology.

[127]  D. Ingber,et al.  Inhibition of angiogenesis through modulation of collagen metabolism. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[128]  G. Schlimok,et al.  Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[129]  T. Powles,et al.  Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases. , 1987, British medical journal.

[130]  J. Coindre,et al.  Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. , 1987, British Journal of Cancer.

[131]  J. Denekamp,et al.  Endothelial proliferation in tumours and normal tissues: continuous labelling studies. , 1984, British Journal of Cancer.

[132]  R. Nicosia,et al.  Angiogenesis-dependent tumor spread in reinforced fibrin clot culture. , 1983, Cancer research.

[133]  P. Saigo,et al.  Axillary Micro- and Macrometastases in Breast Cancer: Prognostic Significance of Tumor Size , 1981, Annals of surgery.

[134]  R. Prescott,et al.  The search for occult metastases in breast cancer: does it add to established staging methods? , 1980, The Australian and New Zealand journal of surgery.

[135]  D. Jones,et al.  Mechanism of the induction of angiogenesis by human neoplastic lymphoid tissue: Studies employing bovine aortic endothelial cells in vitro , 1980, The Journal of pathology.

[136]  D. Jones,et al.  Mechanism of the induction of angiogenesis by human neoplastic lymphoid tissue: Studies on the chorioallantoic membrane (CAM) of the chick embryo , 1980, The Journal of pathology.

[137]  H. Rockette,et al.  Pathologic findings from the national surgical adjuvant breast project (protocol no. 4). V. significance of axillary nodal micro‐ and macrometastases , 1978, Cancer.

[138]  H. Rockette,et al.  Detection and significance of occult axillary node metastases in patients with invasive breast cancer , 1978, Cancer.

[139]  E. Unanue,et al.  Activated macrophages induce vascular proliferation , 1977, Nature.

[140]  R. Evans Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma. , 1977, British Journal of Cancer.

[141]  R. Cabanas,et al.  An approach for the treatment of penile carcinoma , 1977, Cancer.

[142]  L. Liotta,et al.  The significance of hematogenous tumor cell clumps in the metastatic process. , 1976, Cancer research.

[143]  J. Folkman,et al.  Anti‐Angiogenesis: New Concept for Therapy of Solid Tumors , 1972, Annals of surgery.

[144]  R. Hutter,et al.  Significance of Axillary Macrometastases and Micrometastases in Mammary Cancer , 1971, Annals of surgery.

[145]  I. Fidler,et al.  Metastasis: Quantitative Analysis of Distribution and Fate of Tumor Emboli Labeled With 125I-5-Iodo-2′ -deoxyuridine , 1970 .

[146]  J. Folkman,et al.  Tumor Behavior in Isolated Perfused Organs: In Vitro Growth and Metastases of Biopsy Material in Rabbit Thyroid and Canine Intestinal Segment , 1966, Annals of surgery.

[147]  J. Pickren Significance of occult metastases. A study of breast cancer , 1961, Cancer.

[148]  O. Saphir,et al.  Obscure axillary lymph‐node metastasis in carcinoma of the breast , 1948, The American journal of pathology.

[149]  S Paget,et al.  THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST. , 1889 .

[150]  S. Bustin,et al.  Genetic detection of lymph node micrometastases in patients with colorectal cancer , 1998, The British journal of surgery.

[151]  B. Teicher,et al.  Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma , 1996, Cancer Chemotherapy and Pharmacology.

[152]  N. Bouck,et al.  How tumors become angiogenic. , 1996, Advances in cancer research.

[153]  A. Harris,et al.  Mechanisms and therapeutic implications of angiogenesis. , 1996, Current opinion in oncology.

[154]  J. Folkman,et al.  Angiogenesis Inhibitors Generated by Tumors , 1995, Molecular medicine.

[155]  Lars Holmgren,et al.  Dormancy of micrometastases: Balanced proliferation and apoptosis in the presence of angiogenesis suppression , 1995, Nature Medicine.

[156]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[157]  G. Gasparini Quantification of intratumoral vascularization predicts metastasis in human invasive solid tumors (review). , 1994, Oncology reports.

[158]  M. Klagsbrun,et al.  Regulators of angiogenesis. , 1991, Annual review of physiology.

[159]  J. Sloane,et al.  Micrometastases in breast cancer: long-term follow-up of the first patient cohort. , 1991, European journal of cancer.

[160]  S. Friedman,et al.  Importance of tumor cells in axillary node sinus margins ('clandestine' metastases) discovered by serial sectioning in operable breast carcinoma. , 1988, Acta oncologica.