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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. 768 83

Seventy-one patients with untreated hepatocellular carcinoma (111 tumors) were studied angiographically to investigate the pathological features of multiple carcinoma. The 111 tumors comprised 23 lesions resected from 14 patients and 88 lesions measuring 3 cm or less in diameter detected in 57 patients who did not undergo resection. Hemodynamically, major lesions exhibited an increase in frequency of tumor angiogenesis and intensity of tumor stain with an increase in diameter. Analysis of angiographic features of tumors measuring 2 cm or less in diameter revealed a greater vascularity in intrahepatic metastatic foci than in primary foci, demonstrating a difference between them. When multiple tumors were classified into the isolated, concentric or disseminated type in terms of the pattern of their distribution, their angiographic findings suggested that min or lesions of the concentric or disseminated type might represent local metastases spread from the primary focus, and that those of the isolated type might represent multicentric occurrence in the liver.
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PMID:[An angiographic study on the pathological features of multiple hepatocellular carcinoma]. 781 21

Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis.
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PMID:Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. 785 49

Metastatic disease is one of the major causes of death from cancer in human beings. Several enzyme systems have been implicated in the metastatic process, but the metalloproteinases (MPs) appear to be the major group involved in most instances of neoplastic invasion. Increased MP activity has been correlated with the metastatic potential of many cancers, including breast cancer. MPs also play a role in tumor angiogenesis. Tetracyclines are antimicrobial agents that can suppress MP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MPs as well. A synthetic tetracycline, doxycycline, inhibits migration of human MDA-MB-435 breast adenocarcinoma cells through a reconstituted basement membrane (Matrigel), an assay used as an in vitro surrogate for the in vivo process of tumor invasion through basement membranes. Additionally, doxycycline diminishes the proliferation of this breast cancer cell line and also decreases its gelatinolytic activity, as determined by gel zymography.
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PMID:Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells. 789 8

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34-42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent permeability factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth factor in vitro, and it presumably stimulates EC proliferation in vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.
Cancer Metastasis Rev 1993 Sep
PMID:Vascular permeability factor (VPF, VEGF) in tumor biology. 828 15

This presentation explores clinical indications, limitations, and the scientific rationale for use of gadolinium contrast agents in MR imaging of the brain and spine. Enhancement of abnormal CNS tissues is related to structure and function of the blood-brain barrier under pathologic conditions, the prototype of which is tumor angiogenesis. Gadolinium administration can improve the diagnostic sensitivity of intracranial MR imaging, facilitating detection of leptomeningeal or ependymal disease spread and metastases. Moreover, use of contrast often provides greater diagnostic specificity by virtue of the presence and, in many cases, the absence of enhancement. This is particularly helpful in distinguishing metastases from other potential causes of high signal intensity on unenhanced spin-echo (SE) images. In addition to improving diagnosis of neoplasia, gadolinium use is often necessary to demonstrate most cranial neuropathies and to differentiate herniated disc from epidural fibrosis in the failed-back surgery syndrome. Advanced techniques that exploit gadolinium's properties (e.g., MR angiography, perfusion MR imaging) or increase its diagnostic effectiveness (e.g., fat suppression in the postoperative spine) are treated.
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PMID:Rationale and clinical indications for contrast agents in MR imaging of the brain and spine. 848 25

Abundant evidence has shown that tumor growth and metastasis are dependent upon tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within the tumor. Until TA occurs, tumors grow no larger than 2-4 mm in diameter. Also, TA is necessary at the beginning and at the end of the metastatic cascade of events. Thus, it seems reasonable that increasing intratumoral microvascular density (iMVD) might correlate with greater tumor aggressiveness, such as a higher frequency of metastases and/or decreased survival. Indeed, in 1991 my colleagues and I reported a statistically significant association between greater incidence of metastases in patients with breast carcinoma and increasing iMVD. Microvessel density was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density (neovascular "hot spot"). This was done after endothelial cells, lining the microvessels, had been highlighted with anti-factor VIII-related antigen/von Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti-CD31, have shown that the association of greater tumor aggressiveness with increasing iMVD exists not only in breast carcinoma, but also in other solid tumors. This article reviews the methods of highlighting intratumoral vessels and describes the techniques for counting these vessels for assessing iMVD.
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PMID:Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. 853 65

Previous studies have suggested that differential expression and/or activation of integrins facilitates metastatic progression in murine and human melanoma. While recent data show that the integrin alphavbeta3 is involved in tumor angiogenesis and that tumor growth may be abrogated by alphavbeta3 inhibitors in vitro, the clinical significance of beta3 integrin expression in human malignant melanoma is not known. To assess the prognostic value of beta3 integrin expression, we examined primary cutaneous melanomas from 160 patients followed for a mean of 98 months or until death. We quantified the percentage of tumor area stained with beta3 integrin Ab CD-61 using an image analyzer. beta3 integrin expression was detected in 107/160 primary melanomas (69%). beta3-integrin-positive (beta3+) tumors were thicker (mean 2.98 +/- 0.3 mm) than beta3-integrin-negative (beta3-) melanomas (mean 1.64 +/- 0.2 mm) (P = 0.002). Patients with beta3+ melanomas were more likely to relapse (57/107, 53%) and to die from disease (45/107, 42%) than those with beta3- tumors (6/53, 11%; and 4/53, 8%, respectively) (P < 0.001). Overall survival was greater for beta3- than for beta3+ patients (mean 102 +/- 9 vs 69 +/- 6 months) (P = 0.001). These data show that beta3 integrin expression in primary cutaneous melanoma predicts subsequent metastatic progression. Further study of beta3 integrins in the development of melanoma metastases may yield new therapeutic strategies, as well as prognostic information, for the treatment of this cancer.
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PMID:Beta3 integrin expression in melanoma predicts subsequent metastasis. 866 Nov 92

To investigate the correlation between tumor angiogenesis with axillary metastasis in breast cancer, we analyzed a series of 130 cases of infiltrating ductal carcinoma N.O.S. Tissue sections were stained with factor VIII-RA and microvessel quantitation was performed at x 400 magnification in the most vascular areas and expressed in vessels per mm2. Other variables such as tumor size, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, anti-P.C.N.A. (proliferative cell nuclear antigen) and estradiol and progesterone receptors measured by an immunohistochemical method were determined. Statistical analysis of variance (AN-OVA) and Pearson's correlation coefficient were applied. The average of vessels per mm2 in tumors with metastases (n = 70) was 82.0 (median 74, SD 37.5), whereas in tumors without metastases (n = 60), it was 67.1 (median 64, SD 28.1). The difference was statistically significant (p < 0.01). However, the significance was lost when tumor size was introduced as a co-factor in a multifactorial analysis of variance. The number of vessels was unassociated with menopausal status, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, estradiol and progesterone receptors and proliferative activity measured with anti-P.C.N.A. We conclude that in breast ductal invasive carcinoma, when tumor size is taken into consideration, angiogenesis is not associated with axillary lymph node metastases.
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PMID:Microvessel quantitation in breast ductal invasive carcinoma. Correlation with proliferative activity, hormonal receptors and lymph node metastases. 869 12

There are two distinct phases during prostatic carcinogenesis with regard to tumor blood vessel development. During the first or prevascular phase, which may persist for years, cells that have undergone some but not all of the transformation steps undergo a limited amount of net growth, producing premalignant prostatic intraepithelial neoplastic (PIN) lesions. Most of these PIN lesions do not continue net growth and do not progress to produce histologically detectable cancer. Even the PIN lesions that do progress to cancer remain of limited virulence unless they undergo conversion to the second or angiogenic phase. Once this angiogenic phase is reached, new blood vessel development is greatly enhanced within the cancer. It is this enhanced tumor angiogenesis which allows these cancers both to grow continuously and to metastasize. Thus, inhibition of angiogenesis should be an effective chemopreventive approach for prostatic carcinogenesis. Linomide is a low molecular weight, water-soluble agent with excellent p.o. absorption and bioavailability. We have previously demonstrated that daily p.o. treatment with Linomide has antiangiogenic abilities against a series of rat and human prostatic cancer xenografts growing in vivo. In the present studies, we have demonstrated using Matrigel in in vivo angiogenesis assays that daily p.o. Linomide at 25 mg/kg/day inhibits angiogenesis induced by tumor necrosis factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and vascular endothelial growth factor. Using an N-methylnitrosourea initiation-androgen promotion model, Linomide was given p.o. at a daily dose as high as 25 mg/kg/day for at least 1 year without major toxicity while inhibiting the development of seminal vesicle/prostate cancers in male rats by >50%. Dose-response analysis demonstrated that a Linomide blood level of 50-100 microM is optimal for such chemoprevention. In addition, Linomide treatment at a dose of 25 mg/kg/day was able to inhibit by approximately 60% the incidence of N-methylnitrosourea and approximately 50% of 7,12-dimethyl-benz(a)anthracine-induced mammary carcinogenesis in female rats.
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PMID:Antiangiogenic treatment with linomide as chemoprevention for prostate, seminal vesicle, and breast carcinogenesis in rodents. 875 2


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