Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed and evaluated an in vivo athymic nude mouse model for tumor growth, angiogenesis, metastasis, and antineoplastic drug development. Melanoma cell lines expressing beta-galactosidase encoded by the Escherichia coli lac Z gene have been created by infecting an immortal murine melanocyte cell line with a recombinant retrovirus expressing the v-Ha-ras oncogene and lac Z to generate the MRB (melanoma, ras, beta-galactosidase) cell lines. The amelanotic, phorbol ester-independent, transformed melanoma cell lines developed tumors rapidly when injected subcutaneously into nude mice, as well as experimental lung metastases when injected i.v. into the tail vein. beta-galactosidase-expressing subcutaneous tumors and lung metastases stained blue with X-gal. The melanomas produced in nude mice have been characterized by using various histochemical and immunohistochemical staining methods to detect melanoma- and endothelial-cell-specific markers to determine the extent of neovascularization in MRB nude mouse tumors. Optimal staining of endothelial cells involved in tumor angiogenesis was observed by using ADPase activity and antiangiotensin-converting enzyme antibody staining. Attempts at indirect quantification of metastatic tumor cell number within the lung by either beta-galactosidase enzymatic activity or ELISA immunoreactivity were unsuccessful. However, the MRB cell lines should be useful in screening for and studying the mechanisms of action of antineoplastic, antimetastatic, and angiostatic drugs in vivo in athymic nude mice.
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PMID:Evaluation of a nude mouse tumor model using beta-galactosidase-expressing melanoma cells. 768 92

To clarify the correlation between tumor angiogenesis and tumor growth in head and neck carcinomas, we investigated the number of microvessels, using immunohistochemical factor VIII. No correlations among this number, differences in the primary lesion, histological differentiation and T classification were detected. The incidence of neck lymph node metastases increased as microvessel numbers increased in tumor sites. The number of microvessels increased as N and Stage classification progressed. The number of microvessels in CR cases after induction chemotherapy were increased. The numbers of microvessels in patients without recurrence were apparently greater than those in patients with recurrence. The results of this study suggest that the number of microvessels in a primary tumor correlates with the metastatic ability of the tumor.
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PMID:[Angiogenesis in head and neck tumor]. 768 79

Human hepatocellular carcinoma (HCC) is characterized by hypervascularity and tumor staining in angiograms, and tumor angiogenesis is considered indispensable for tumor growth. HCC is also characterized by an obvious multistage process of tumor progression. To find out in which stage of human hepatocarcinogenesis angiogenesis occurs, we have carried out a pathological study, of the phenotypic changes in tumor vessels taken from surgically resected liver tumors showing each step of the progression. Eleven early advanced HCCs (advanced HCC component in early HCC nodule, eAd HCC), seven early HCCs (eHCC) and six adenomatous hyperplasias (AH), the non-tumorous liver surrounding each and five normal livers were studied by lectin histochemistry and immunohistochemistry. The sinusoidal endothelial cells from the non-tumorous liver were shown to be negative for UEA-I (Ulex europaeus I), but the endothelial cells from the sinusoidal tumor vessels in advanced HCC components were strongly positive. In AH and eHCC, half the tumors were negative and the other half focally positive. In the early HCC lesion of eAdHCC, the rate of positivity for UEA-I was a little higher than in AH and eHCC but lower than in advanced HCC lesions in eAdHCC. Immunohistochemically, laminin was not detected in the sinusoids in the non-tumorous liver or in the sinusoidal tumor vessels in AH and eHCC. In eAdHCC, however, two early HCC lesions and four advanced HCC lesions were positive. An immunohistochemical examination for muscle actin revealed an increase in arterial tumor vessels in six advanced HCC lesions and one early HCC lesion of eAdHCC. The results indicate the emergence of UEA-I-positive sinusoidal tumor vessels to be most pronounced during the progression from eHCC to advanced HCC, and laminin-positive sinusoidal tumor vessels or actin-positive arterial tumor vessels to emerge mainly in advanced HCC.
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PMID:Phenotype changes in tumor vessels associated with the progression of hepatocellular carcinoma. 768 37

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.
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PMID:Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003. 792 32

Polypeptide growth factors contribute to the development and maintenance of normal tissues and are essential for the growth and metastasis of solid tumors. During tumor progression these factors function as autocrine stimulators of tumor cells and/or serve to recruit stromal tissue and blood supply to the expanding tumor. In particular, tumor-induced angiogenesis appears to be significant not only for local tumor growth but also for metastasis to distant organ sites. We purified several years ago the heparin-binding growth factor pleiotrophin (PTN) from the supernatants of human breast cancer cells and demonstrated that PTN can serve as an angiogenesis factor. We found the gene expressed in a number of human tumor cell lines as well as in human tumor tissues. Here we present different approaches to inhibit production and function of this growth factor. Finally we discuss how the experience from this growth factor can be applied to improve our understanding of the role of other factors thought to contribute to tumor angiogenesis.
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PMID:Molecular and pharmacologic targeting of angiogenesis factors--the example of pleiotrophin. 853 64

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

The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm2 in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm2 (p < 0.00001). The significance of MVD was found in both node-negative and node-positive patients (p < 0.005 and p < 0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p < 0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p < 0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p < 0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.
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PMID:Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. 853 67

Irsogladine used clinically as an anti-gastric ulcer agent, at 10(-6)-10(-4)M, inhibited cell proliferation and tubular morphogenesis of vascular endothelial cells, but the proliferation of human epidermoid cancer or glioma cells was not inhibited by this drug, even at 10(-4)M. In vivo studies demonstrated that p.o. administration of irsogladine significantly inhibited tumor growth of human glioma cells in mice, and histological analysis showed a dramatic decrease of the neovascularization in the tumors. In mice transplanted with chambers containing human glioma cells or hepatic cancer cells, irsogladine also inhibited angiogenesis. These in vivo and in vitro assays demonstrate that irsogladine may be a unique and potent inhibitor of tumor angiogenesis.
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PMID:Inhibition of tumor growth and neovascularization by an anti-gastric ulcer agent, irsogladine. 860 95

Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume. Several growth factor receptor tyrosine kinases have been implicated in angiogenesis, including receptors for epidermal, fibroblast, and platelet-derived growth factors, as well as the receptors Flk-1/KDR, Flt-1 Tek/Tie-2, and Tie-1. Endothelial cells in the vessels of tumors express Flk-1/KDR, a receptor for vascular endothelial growth factor. Flk-1 was previously shown to play a role in angiogenesis and tumor formation of s.c. xenografts of C6 glioma cells using dominant-negative methodology. We now demonstrate that Flk-1 seems to be generally involved in the growth of a wide range of solid tumors, including mammary, ovarian, and lung carcinoma, as well as glioblastoma. Furthermore, survival times in rats bearing intracerebral tumors were prolonged using the same dominant-negative methodology. The involvement of Flk-1 in a variety of tumor types suggests an important role for Flk-1 in tumor angiogenesis.
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PMID:Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. 860 10

Mutations or loss of both alleles of the von Hippel-Lindau (VHL) tumor suppressor gene has been documented in sporadic renal cell carcinomas and neoplasms that arise in individuals having the VHL syndrome. The well-vascularized phenotype of tumors that form in VHL disease let us consider vascular endothelial growth factor (VEGF) as a mediator of tumor growth in VHL disease. Human renal carcinoma cells that either lacked endogenous wild-type VHL or were transfected with an inactive mutant VHL showed deregulated expression of VEGF on the mRNA and protein level that was reverted by introduction of wild-type VHL. Stimulation of proliferation of endothelial cells by conditioned medium of cells expressing mutant VHL was almost abolished by neutralizing the VEGF. In contrast, expression of basic fibroblast growth factor and of c-myc proto-oncogene was not affected by VHL. Our data suggest VEGF as the key tumor angiogenesis factor in VHL disease.
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PMID:Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein. 862 3


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