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Noel Weidner - One of the best experts on this subject based on the ideXlab platform.
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angiogenesis in bladder cancer relationship between Microvessel density and tumor prognosis
Journal of the National Cancer Institute, 1995Co-Authors: Bernard H Bochner, Noel Weidner, Richard J Cote, Susan Groshen, Su Chiu Chen, Donald G Skinner, Peter W NicholsAbstract:Background : Tumor stage, histologic grade, and regional lymph node status are currently used to obtain prognostic information about bladder cancers. However, additional prognostic indicators are needed to aid clinicians in selecting patients who would benefit most from specific therapies. A majority of studies assessing the prognostic value of measuring tumor angiogenesis (i.e., measurement of tumor Microvessel densities) have found a positive association between increasing Microvessel densities and worsening prognosis. Purpose : We explored the relationship between established prognostic indicators and the extent of tumor-associated angiogenesis in patients with invasive transitional cell carcinoma (TCC) of the bladder, and we determined whether tumor Microvessel density measurement could be used independently to predict bladder tumor behavior. Methods : Tumor tissue was obtained from 164 patients with invasive primary TCC of the bladder. The extent of tumor-associated angiogenesis in this tissue was evaluated by immunohistochemical methods using HPCA-1, a mouse monoclonal antibody directed against the endothelial cell antigen, CD34. The number of Microvessels in a 200x microscopic high-power field (hpf) containing the area of greatest neovascularization within or immediately adjacent to each tumor was determined. The patient population was then divided into three equivalently sized groups, with tumors containing low (≤64), intermediate (65-99), or high (≥100) numbers of Microvessels per hpf. Kaplan-Meier product limit estimates of overall survival and the complement of cumulative incidence curves for recurrence-free survival were plotted. When analyzing survival or recurrence, the logrank test was used to compare groups of patients with and without stratification according to tumor stage. Analysis of variance was used to test for an association between Microvessel density and established prognostic variables. Reported P values are from two-sided tests. Results : Microvessel density was significantly associated with disease-free (P<.0001) and overall (P =.0007) survival. The estimated probabilities of recurrence at 5 years were 19% (95% confidence interval [CI] = 8-29), 56% (95% CI = 43-69), and 68% (95% CI = 55-81) for patients with lowest, intermediate, and highest Microvessel counts, respectively. Overall survival at 5 years was estimated to be 68% (95% CI = 56-81), 44% (95% CI = 30-57), and 34% (95% CI = 21-47) for the same three patient groups. Microvessel density was associated with disease progression in patients with organ-confined tumors, tumors extending through the bladder wall, and tumors that had spread to regional lymph nodes. Tumor angiogenesis was found to be an independent prognostic indicator when evaluated in the presence of histologic grade, pathologic stage, and regional lymph node status. Conclusion : Tumor angiogenesis, as determined by Microvessel density measurement, is an independent prognostic indicator for patients with invasive TCC of the bladder.
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tumor angiogenesis correlates with metastasis in invasive prostate carcinoma
American Journal of Pathology, 1993Co-Authors: Noel Weidner, John Flax, Peter R Carroll, W. Blumenfeld, J FolkmanAbstract:Tumor growth and metastasis require angiogenesis; and Microvessel density, a measure of tumor angiogenesis, correlates with metastasis in breast and lung carcinoma. To determine how Microvessel density correlated with metastasis in prostate carcinoma, we counted Microvessels within the initial invasive carcinomas of 74 patients (29 with metastasis, 45 without). Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Without knowledge of the patient's cancer stage, Microvessels were counted in a 200 field (0.739 mm2) in the most active areas of neovascularization. The mean Microvessel count in tumors from patients with metastases was 76.8 Microvessels per 200 field (median, 66; standard deviation, 44.6). The counts within carcinomas from patients without metastasis were significantly lower, 39.2 (median, 36; standard deviation, 18.6) (P < 0.0001). Microvessel counts increased with increasing Gleason's score (P < 0.0001), but this increase was present predominantly in the poorly differentiated tumors. Although Gleason's score also correlated with metastasis (P = 0.01), multivariate analysis showed that Gleason's score added no additional information to that provided by Microvessel count alone. Assay of Microvessel density within invasive tumors may prove valuable in selecting patients for aggressive adjuvant therapies in early prostate carcinoma.
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tumor angiogenesis a new significant and independent prognostic indicator in early stage breast carcinoma
Journal of the National Cancer Institute, 1992Co-Authors: Noel Weidner, Judah Folkman, F Pozza, P Bevilacqua, Elizabeth N Allred, Dan H Moore, S Meli, Giampietro GaspariniAbstract:BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that Microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE This study was designed to further define the relationship of Microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS In a prospective, blinded study of 165 consecutive patients, the Microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted Microvessels per 200x field in the most active areas of neovascularization and graded Microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS There was a highly significant (P < or = .001) association of Microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 Microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer Microvessels per 200x field. Moreover, Microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only Microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.
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tumor angiogenesis and metastasis correlation in invasive breast carcinoma
The New England Journal of Medicine, 1991Co-Authors: Noel Weidner, Joseph P Semple, William R Welch, Judah FolkmanAbstract:Abstract Background. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted Microvessels (capillaries and venules) and graded the density of Microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). Methods. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocyto-chemically for factor VIII. The Microvessels were carefully counted (per 200×field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. Results. Both Microvessel counts and density grades correlated with metastatic disease. The mean (±SD) count and grade in the patients with metastases were 101±49.3 and 2.95±1.00 vessels, respect...
G Perry - One of the best experts on this subject based on the ideXlab platform.
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Serial reconstruction of beta-protein amyloid plaques: relationship to Microvessels and size distribution.
Brain research, 1992Co-Authors: M Kawai, P Cras, G PerryAbstract:The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from Microvessels is mainly based on the finding that many plaques are topographically associated with Microvessels. However, because the Microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with Microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and Microvessels with antibodies raised against beta-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 microns thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 microns were associated with Microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with Microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.
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Serial reconstruction of β-protein amyloid plaques: relationship to Microvessels and size distribution
Brain Research, 1992Co-Authors: M Kawai, P Cras, G PerryAbstract:Abstract The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from Microvessels is mainly based on the finding that many plaques are topographically associated with Microvessels. However, because the Microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with Microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and Microvessels, with antibodies raised against β-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 μm thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 μm were associated with Microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with Microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.
William P Collins - One of the best experts on this subject based on the ideXlab platform.
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Expression of thymidine phosphorylase in malignant ovarian tumors: correlation with Microvessel density and an ultrasound‐derived index of angiogenesis
Ultrasound in Obstetrics & Gynecology, 1998Co-Authors: Kohkichi Hata, Hiroaki Nagami, K Miyazaki, Kohji Iida, William P CollinsAbstract:Objective The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of Microvessels within the tumor, and with ultrasound-derived indices of blood flow. Methods Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of Microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the Microvessel count and the peak systolic velocity (PSV). Results Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for Microvessel count and PSV were similar. The Microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the Microvessel count and the PSV (r = 0.354, p = 0.022). Conclusions The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in Microvessel density and PSV in patients with ovarian cancer. Copyright © 1998 International Society of Ultrasound in Obstetrics and Gynecology
Judah Folkman - One of the best experts on this subject based on the ideXlab platform.
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Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumours
The Lancet, 1994Co-Authors: Judah Folkman, Rebecca D. Folkerth, R M Scott, Mcl P Black, Patrick D Barnes, Stephen E Sallan, Maria Rupnick, Hidemi WatanabeAbstract:Abstract Summary Tumour growth is angiogenesis-dependent; brain tumours have more intense neovascularisation than other tumours and produce basic fibroblast growth factor, a potent angiogenic mediator. Because little is known about the release of basic fibroblast growth factor from brain tumours into extracellular fluids, we tested cerebrospinal fluid (CSF) from 26 children and young adults with brain tumours and 18 controls for basic fibroblast growth factor and for proliferative activity on cultured capillary endothelial cells. We also measured the density of Microvessels in tumours by immunohistochemical staining. Basic fibroblast growth factor was detected in the CSF of 62% (16 of 26) patients with brain tumours but in none of the controls. Specimens with basic fibroblast growth factor stimulated DNA synthesis of capillary endothelial cells in vitro. Endothelial proliferative activity was blocked by neutralising antibodies to basic fibroblast growth factor. Basic fibroblast growth factor correlated with mitogenic activity in CSF in vitro (p0·0001), and with density of Microvessels in histological sections (p0 005). A Microvessel count of ≽68 per 200 × field was associated with tumour recurrence (p=0·005) and with mortality (p=0·02). Basic fibroblast growth factor in brain tumours may mediate angiogenesis as measured by Microvessel density in histological sections, so has potential as both a marker for neoplasia and a target for tumour treatments. Furthermore, evaluation of cerebrospinal fluid basic fibroblast growth factor, along with Microvessel quantitation in biopsied tumours, may provide improved prognostic information for the management of patients with brain tumours.
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tumor angiogenesis a new significant and independent prognostic indicator in early stage breast carcinoma
Journal of the National Cancer Institute, 1992Co-Authors: Noel Weidner, Judah Folkman, F Pozza, P Bevilacqua, Elizabeth N Allred, Dan H Moore, S Meli, Giampietro GaspariniAbstract:BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that Microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE This study was designed to further define the relationship of Microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS In a prospective, blinded study of 165 consecutive patients, the Microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted Microvessels per 200x field in the most active areas of neovascularization and graded Microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS There was a highly significant (P < or = .001) association of Microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 Microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer Microvessels per 200x field. Moreover, Microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only Microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.
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tumor angiogenesis and metastasis correlation in invasive breast carcinoma
The New England Journal of Medicine, 1991Co-Authors: Noel Weidner, Joseph P Semple, William R Welch, Judah FolkmanAbstract:Abstract Background. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted Microvessels (capillaries and venules) and graded the density of Microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). Methods. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocyto-chemically for factor VIII. The Microvessels were carefully counted (per 200×field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. Results. Both Microvessel counts and density grades correlated with metastatic disease. The mean (±SD) count and grade in the patients with metastases were 101±49.3 and 2.95±1.00 vessels, respect...
M Kawai - One of the best experts on this subject based on the ideXlab platform.
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Serial reconstruction of beta-protein amyloid plaques: relationship to Microvessels and size distribution.
Brain research, 1992Co-Authors: M Kawai, P Cras, G PerryAbstract:The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from Microvessels is mainly based on the finding that many plaques are topographically associated with Microvessels. However, because the Microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with Microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and Microvessels with antibodies raised against beta-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 microns thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 microns were associated with Microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with Microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.
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Serial reconstruction of β-protein amyloid plaques: relationship to Microvessels and size distribution
Brain Research, 1992Co-Authors: M Kawai, P Cras, G PerryAbstract:Abstract The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from Microvessels is mainly based on the finding that many plaques are topographically associated with Microvessels. However, because the Microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with Microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and Microvessels, with antibodies raised against β-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 μm thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 μm were associated with Microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with Microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.