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Angiogenesis

About: Angiogenesis is a research topic. Over the lifetime, 58248 publications have been published within this topic receiving 3290129 citations. The topic is also known as: blood vessel formation from pre-existing blood vessels & GO:0001525.


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TL;DR: It is suggested that leukemia cells induce angiogenesis in the bone marrow and that leukemia might be angiogenic dependent and raise the possibility for a role of antiangiogenic drugs in the treatment of leukemia.
Abstract: It has been shown that solid tumors progress in concert with an induction of tumor angiogenesis. It is not known, however, whether a similar phenomenon occurs in leukemia. Angiogenesis was characterized immunohistochemically by factor VIII staining of bone marrow biopsies and quantified by assessment of microvessel density using previously described techniques. We evaluated bone marrow biopsies from 40 children with newly diagnosed, untreated acute lymphoblastic leukemia. In 22 of the patients, we also evaluated angiogenesis after the completion of remission induction chemotherapy. Control specimens were obtained from children undergoing staging evaluations at the time of diagnosis of solid tumors and lymphomas. Microvessels were counted throughout the entire core specimen in consecutive x 200 fields, and a median count per field (cpf) was calculated. In addition, the number of microvessels in the single x 200 field with the highest microvessel density was designated as the "hot spot." Biopsies from children with leukemia and from controls showed median microvessel densities of 42 and 6 counts per field, respectively (P < or = 0.0001). Microvessel density of the hot spots of leukemia specimens and controls were also significantly different, 51 and 8, respectively (P < or = 0.0001). A computer-aided three-dimensional reconstruction model of bone marrow vascularity showed a complex, arborizing branching of microvessels in leukemic specimens compared with single, straight microvessels without branching in controls. Urinary basic fibroblast growth factor, a potent angiogenic factor, was measured in 22 of the children with newly diagnosed leukemia and in 39 normal, age-matched controls. Urinary basic fibroblast growth factor levels were increased in all 22 patients before treatment, were variable during induction chemotherapy, and demonstrated statistically insignificant decreases at the time of complete remission. These findings suggest that leukemia cells induce angiogenesis in the bone marrow and that leukemia might be angiogenesis dependent and raise the possibility for a role of antiangiogenic drugs in the treatment of leukemia.

554 citations

Journal ArticleDOI
TL;DR: This finding, that circulating EPCs may home to sites of neovascularization and differentiate into endothelial cells in situ, is consistent with "vasculogenesis," a critical paradigm for embryonic nevascularization, and suggests that vasculogenesis and angiogenesis may constitute complementary mechanisms for postnatal neov vascularization.
Abstract: In the past decade, researchers have defined committed stem or progenitor cells from various tissues, including bone marrow, peripheral blood, brain, liver, and reproductive organs, in both adult a...

554 citations

Journal ArticleDOI
Judah Folkman1
TL;DR: The first angiogenesis inhibitors for cancer have now been approved by the F.D.A. in the U.S. and in 28 other countries, including China as mentioned in this paper.

553 citations

Journal ArticleDOI
TL;DR: In this paper, the authors investigated whether the level of HIF-1α is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers, such as vascular endothelial growth factor (VEGF), HER-2/neu, p53, Ki-67, and estrogen receptor (ER).
Abstract: Background: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases. In this report, we investigated whether the level of HIF-la is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers. Methods: Paraffin-embedded clinical specimens from five pathologic stages of breast tumorigenesis and from normal breast tissue were used. HIF-1α protein and the biomarkers vascular endothelial growth factor (VEGF), HER-2/neu, p53, Ki-67, and estrogen receptor (ER) were identified immunohistochemically, and microvessel density (a measure of angiogenesis) was determined. Associations among levels of HIF-la and these biomarkers were tested statistically. All statistical tests are two-sided. Results: The frequency of HIF-1α-positive cells in a specimen increased with the specimen's pathologic stage (P<.001, X 2 test for trend) as follows: normal breast tissue (0 specimens with ≥1% HIF-1α-positive cells in 10 specimens tested), ductal hyperplastic lesions (0 in 10), well-differentiated ductal carcinomas in situ (DCIS) (11 in 20), well-differentiated invasive breast cancers (12 in 20), poorly differentiated DCIS (17 in 20), and poorly differentiated invasive carcinomas (20 in 20). Increased levels of HIF-la were statistically significantly associated with high proliferation and increased expression of VEGF and ER proteins. In DCIS lesions, increased levels of HIF-1α were statistically significantly associated with increased microvessel density. HIF-la showed a borderline association with HER-2/neu but no association with p53. Conclusions: The level of HIF-la increases as the pathologic stage increases and is higher in poorly differentiated lesions than in the corresponding type of well-differentiated lesions. Increased levels of HIF-1α are associated with increased proliferation and increased expression of ER and VEGF. Thus, increased levels of HIF-la are potentially associated with more aggressive tumors.

553 citations

Journal ArticleDOI
TL;DR: The potential for development of c-Met inhibitors for treatment of human cancers is addressed with particular emphasis on recent findings with small-molecule inhibitors.

552 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
20234,761
20225,433
20212,598
20202,542
20192,517