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Results for “Neovascularization, Pathologic”

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PubMed1988

The development of vitreous membranes and retinal detachment induced by intravitreal carbon microparticles.

We induced intravitreal cellular proliferation by injection of carbon microparticles (size 20-70 nm) into the vitreous of 21 eyes of 11 cynomolgus monkeys. Pathological changes were evaluated by light and electron microscopy. At 1 week, there was conspicuous cyclitis showing exudative separation of the nonpigmented and pigmented ciliary epithelium, inflammatory cells, mononuclear phagocytes, and premacular vitreous detachment. At 3 weeks, continued macrophagic response was accompanied by fibrovascular proliferation with ingrowth of vessels from the ciliary body into the vitreous. At 4-5 weeks, deposition of extracellular fibrous material and traction retinal detachment (RD) were found. At 10 weeks, all eyes had extensive RD with pre- and subretinal collagenous cellular membranes. Carbon-laden macrophages were aggregated over the optic disc and fovea with prepapillary neovascularization and cystoid macular edema. Thus, intravitreal fibrovascular proliferation, vitreous contraction, and RD were induced by inflammatory and phagocytic response to carbon particles.

Animals↗

PubMed1995

Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer.

This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twenty-five patients had stage I disease, eight patients had stage II disease, and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM-1). The microvessels in the areas of highest neovascularization were counted under light microscopy in 200x field by two independent observers without knowledge of clinical information. At least three separate fields were counted for each specimen. The Mann-Whitney U test was used for statistical analysis. The microvessel counts in adenocarcinoma were significantly higher than in the squamous cell carcinoma (54.4 +/- 35.65 versus 26.16 +/- 20.46 in factor VIII staining and 80.52 +/- 48.42 versus 40.04 +/- 32.33 in PECAM-1 staining; p < 0.001). The microvessel counts in patients with Stages I-II disease were significantly lower than that of stages IIIA-IIIB disease (23.63 +/- 16.21 versus 65.36 +/- 31.92 in factor VIII staining and 41.85 +/- 36.76 versus 93.00 +/- 43.08 in PECAM-1; p < 0.001). Patients with nodal metastasis had higher microvessel density than those without nodal metastasis (56.67 +/- 35.55 versus 23.44 +/- 15.77 in factor VIII staining and 86.89 +/- 46.46 versus 36.30 +/- 25.83 in PECAM-1 staining; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed2006

The duality of angiogenesis: implications for therapy of human disease.

Angiogenesis, the development of a microvasculature to a neoplastic, inflammatory, or infectious disease process, is a promising therapeutic target for disease therapy that has not been fully exploited. To further understand angiogenesis and its potential for therapy of dermatologic disorders, one must understand the many dualities of pathologic angiogenesis. These dualities are direct versus indirect angiogenesis inhibition, the differing origins of endothelial cells, which may arise either locally or through bone marrow stem cells, and regulation of vascular endothelial growth factor (VEGF) by hypoxia-dependent and/or independent pathways. The future development of therapy directed at pathologic angiogenesis is dependent upon an understanding of the factors that regulate angiogenesis. The presence of both direct and indirect inhibition of angiogenesis, the multiple sources of endothelial cells, and the regulation of VEGF by hypoxia-independent and/or-dependent pathways must taken into consideration if the promise of effective therapy of human disease is to be realized.

Animals↗

PubMed2001

Systematic evolution of a DNA aptamer binding to rat brain tumor microvessels. selective targeting of endothelial regulatory protein pigpen.

Tumor microvessels differ in structure and metabolic function from normal vasculature, and neoangiogenesis is associated with quantitative and qualitative changes in expression of endothelial proteins. Such molecules could serve as molecular addresses differentiating the tumor vasculature from those of the normal brain. We have applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) against transformed endothelial cells as a complex target to select single-stranded DNA-ligands (aptamers) that function as histological markers to detect microvessels of rat experimental glioma, a fatal brain tumor that is highly vascularized. Both the SELEX selection procedure as well as subsequent deconvolution-SELEX were analyzed by fluorescence based methods (flow cytometry and fluorescence microscopy). Of 25 aptamers analyzed, one aptamer was selected that selectively bound microvessels of rat brain glioblastoma but not the vasculature of the normal rat brain including peritumoral areas. The molecular target protein of aptamer III.1 was isolated from endothelial cells by ligand-mediated magnetic DNA affinity purification. This protein was identified by mass spectrometry as rat homologue of mouse pigpen, a not widely known endothelial protein the expression of which parallels the transition from quiescent to angiogenic phenotypes in vitro. Because neoangiogenesis, the formation of new blood vessels, is a key feature of tumor development, the presented aptamer can be used as a probe to analyze pathological angiogenesis of glioblastoma. The presented data show that pigpen is highly expressed in tumor microvessels of experimental rat brain glioblastoma and may play an important role in warranting blood supply, thus growth of brain tumors.

Animals↗

PubMed2000

Fractals and cancer.

Recent studies have shown that fractal geometry, a vocabulary of irregular shapes, can be useful for describing the pathological architecture of tumors and, perhaps more surprisingly, for yielding insights into the mechanisms of tumor growth and angiogenesis that complement those obtained by modern molecular methods. This article outlines the basic methods of fractal geometry and discusses the value and limitations of applying this new tool to cancer research.

Algorithms↗

PubMed2001

Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis.

Vascular endothelial growth factor (VEGF) and its two receptors, Fms-like tyrosine kinase 1 (Flt-1) (VEGFR-1) and KDR/Flk-1 (VEGFR-2), have been demonstrated to be an essential regulatory system for blood vessel formation in mammals. KDR is a major positive signal transducer for angiogenesis through its strong tyrosine kinase activity. Flt-1 has a unique biochemical activity, 10-fold higher affinity to VEGF, whereas much weaker tyrosine kinase activity compared with KDR. Recently, we and others have shown that Flt-1 has a negative regulatory function for physiological angiogenesis in the embryo, possibly with its strong VEGF-trapping activity. However, it is still open to question whether the tyrosine kinase of Flt-1 has any positive role in angiogenesis at adult stages. In this study, we examined whether Flt-1+ could be a positive signal transducer under certain pathological conditions, such as angiogenesis with tumors overexpressing a Flt-1-specific, VEGF-related ligand. Our results show clearly that murine Lewis lung carcinoma cells overexpressing placenta growth factor-2, an Flt-1-specific ligand, grew in wild-type mice much faster than in Flt-1 tyrosine kinase domain-deficient mice. Blood vessel formation in tumor tissue was higher in wild-type mice than in Flt-1 tyrosine kinase-deficient mice. On the other hand, the same carcinoma cells overexpressing VEGF showed no clear difference in the tumor growth rate between these two genotypes of mice. These results indicate that Flt-1 is a positive regulator using its tyrosine kinase under pathological conditions when the Flt-1-specific ligand is abnormally highly expressed. Thus, Flt-1 has a dual function in angiogenesis, acting in a positive or negative manner in different biological conditions.

Animals↗

PubMed2002

[Neoplasms and angiogenesis].

Angiogenesis is a process of new blood vessels formation in many physiological and pathological conditions such as wound healing, cancer, ischaemic diseases (of heart or limb) and chronic inflammations. Neoplastic angiogenesis plays an important role in progression of the disease and development of metastases. The angiogenic process may be initiated by hypoxia in cancerous cells, mutations in suppressor genes or oncogenes. Cancer cells activate specific angiogenic factors mainly vasoendothelial growth factor (VEGF) that stimulate migration and division of vascular endothelial cells. The studies of several pro- and antiangiogenic molecules and factors, and mechanism of vessel growth, have revealed that therapeutic interferences with these processes offers a tool for clinical applications in various pathologies. Inhibition of angiogenesis can prevent diseases with excessive vessel growth such as, particularly, cancers. Stimulation of angiogenesis can be beneficial in the treatment of diseases such as coronary disease and limb ischaemia. In this article some aspects are presented of current knowledge of angiogenesis and its regulation.

Angiogenesis Inducing Agents↗

PubMedDate not supplied

[Fluorescein iridography in post-thrombotic retinopathy].

Fluorescent iridography evidenced that postthrombotic retinopathy is associated with pathologic changes in the iridal vessels, increase of the circulation time, impaired angioarchitectonics, development of shunts and collaterals, in some cases of new vessels. The degree of the pathologic changes in the iris correlates with the severity of the underlying condition. Extravasal release of fluorescein from the iridal and ciliary vessels evidences an impairment of the permeability of the anterior section of the ++hemato-ophthalmic barrier in postthrombotic retinopathy.

Adult↗

PubMed1998

Systemic sclerosis stimulates angiogenesis in the chick embryo chorioallantoic membrane.

Skin biopsies from patients with systemic sclerosis (SSc) were investigated for their angiogenic activity by using the chick embryo chorioallantoic membrane (CAM) assay. Ten samples of SSc and 10 of normal skin from age- and sex-matched subjects were grafted onto the CAM, and the angiogenic response in pathological and control implants was assessed on histological sections by a planimetric point-count method 4 days after grafting. The vascular counts in the area underlying the SSc were significantly higher than those of normal skin and a dense mononuclear cell infiltrate was detectable around the blood vessels in pathological specimens. These results suggest that SSc may promote angiogenesis, perhaps leading to the release of several angiogenic factors. Moreover, the role played in the angiogenic response by the inflammatory cells forming the cellular infiltrate is suggested by this study.

Adult↗

PubMed2001

Prognostic and predictive factors in prostate cancer.

Prostate cancer is a major public health problem in the Western world, and the second most common male malignancies in the European Union. Detection of the disease is possible at an early stage, using serum prostate specific antigen measurement and prostatic biopsies. To date, however, screening for prostate cancer has not been shown to be of benefit to patients in improving outcome. This is compounded by uncertainties surrounding treatment efficacy, as more men appear to die with prostate cancer than from it. Studies addressing these issues are underway in Europe and the U.S.A. Clinicians are currently unable to advise their patients with any degree of certainty as to the appropriateness of treatment for prostate cancer, because of their inability to differentiate tumours that will progress from those that will remain quiescent. This article reviews the various clinical, pathological and experimental markers available, and their value in providing prognostic information, which may assist clinicians and patients in making management decisions. Further research is still required to understand the biological behaviour of prostate cancer and to assess the value of screening and treatment efficacy in order to advise patients, clinicians and health care systems accordingly.

Apoptosis↗

PubMedDate not supplied

Blood supply and vasculature of mycetoma.

The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.

Arteries↗

PubMed2003

Evaluation of a protocol for examining nephrectomy specimens with renal cell carcinoma.

AIMS: To evaluate the practicality of use and the effectiveness of a standard protocol for examining nephrectomy specimens for renal cell carcinoma (RCC), with emphasis on the identification of vascular invasion. METHODS: A standard protocol, devised to identify the major prognostic determinants, was used to examine 79 consecutive tumours submitted to four histopathology departments. The incidence of vascular invasion found was compared with the incidence in a historical series of tumours. RESULTS: The protocol proved easy to follow, and appeared to increase the incidence of observed vascular invasion (40 of 69 cases compared with 69 of 176 cases in the historical series; p = 0.059, Fishers exact test, one sided) CONCLUSIONS: If pathological prognostic determinants are to be used for clinical management, then it is important that they are identified and recorded consistently. The protocol described provides a method of examining nephrectomy specimens that can be used in routine practice and would probably reliably identify recognised prognostic variables.

Carcinoma, Renal Cell↗

PubMed2006

Noninvasive MRI of endothelial cell response to human breast cancer cells.

We have developed a noninvasive magnetic resonance imaging (MRI) assay to characterize human umbilical vein endothelial cell (HUVEC) motility, invasion, and network formation in response to the presence of cancer cells. HUVECs were labeled with a superparamagnetic iron oxide T(2) contrast agent and cocultured with MDA-MB-231 breast cancer cells in the presence of an extracellular matrix (ECM) gel. Invasion into the ECM gel by HUVECs in response to paracrine factors secreted by MDA-MB-231 cancer cells, as well as network formation by HUVECs, was easily tracked with MRI. The invasive behavior of HUVECs was not observed in the absence of cancer cells. This noninvasive assay used to characterize the response of endothelial cells (ECs) can be used to understand the role of proangiogenic or antiangiogenic stimuli, and to study the interactions between ECs and other disease-specific cells in pathologies with aberrant angiogenesis, such as retinopathy and arthritis.

Adenocarcinoma↗

PubMed1998

Angiogenesis in hepatocellular carcinoma: an experimental study in the chick embryo chorioallantoic membrane.

Ten samples of human hepatocellular carcinoma and three of a laceration injure of the liver (controls) were grafted onto the chick embryo chorioallantoic membrane (CAM) to investigate their possible angiogenic activity. The angiogenic response in pathological and control implants was assessed on histologic sections by a morphometric method, 4 days after grafting. The vascular count in the CAMs treated with the pathological implants was significantly higher compared to control ones and the angiogenic response induced by pathological implants was comparable to that of a well known angiogenic molecule, namely basic fibroblast growth factor. The role played in vasoproliferative response by angio-genic cytokines released by tumor cells, by CAM extracellular matrix and by the perivascular mononuclear cells was supported by this study.

Allantois↗

PubMed2001

[Expression of vascular endothelial growth factor in oral squamous cell carcinoma].

OBJECTIVE: The aim of this study was to estimate the expression of vascular endothelial growth factor(VEGF) and intratumoral microvessel density (IMVD) in oral squamous cell carcinoma(SCC). METHODS: A total of 60 cases of oral squamous carcinoma were immunohistochemically stained with a SP method by using monoclonal antibodies of VEGF and CD34. RESULTS: There was no significant difference in the expression of VEGF in different TNM stages and lymphe node metastases of oral squamous cell carcinoma. The expression of VEGF showed no relation with pathologic grades, but IMVD expression differed significantly in SCC. The carcinoma in grade I and IV of IMVD differed significantly in expression of VEGF. CONCLUSION: It indicates the change of IMVD may resulted from the change of VEGF in oral SCC.

Adult↗

PubMed1995

Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors.

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.

Breast Neoplasms↗

PubMed2006

Vascular endothelial growth factor receptors: molecular mechanisms of activation and therapeutic potentials.

Angiogenesis-associated eye diseases are among the most common cause of blindness in the United States and worldwide. Recent advances in the development of angiogenesis-based therapies for treatment of angiogenesis-associated diseases have provided new hope in a wide variety of human diseases ranging from eye diseases to cancer. One group of growth factor receptors critically implicated in angiogenesis is vascular endothelial growth factor receptors (VEGFR), a subfamily of receptor tyrosine kinases (RTKs). VEGFR-1 and VEGFR-2 are closely related receptor tyrosine kinases and have both common and specific ligands. VEGFR-1 is a kinase-impaired RTK and its kinase activity is suppressed by a single amino acid substitution in its kinase domain and by its carboxyl terminus. VEGFR-2 is highly active kinase, stimulates a variety of signaling pathways and broad biological responses in endothelial cells. The mechanisms that govern VEGFR-2 activation, its ability to recruit signaling proteins and to undergo downregulation are highly regulated by phosphorylation activation loop tyrosines and its carboxyl terminus. Despite their differential potentials to undergo tyrosine phosphorylation and kinase activation, both VEGFR-1 and VEGFR-2 are required for normal embryonic development and pathological angiogenesis. VEGFR-1 regulates angiogenesis by mechanisms that involve ligand trapping, receptor homodimerization and heterodimerization. This review highlights recent insights into the mechanism of activation of VEGFR-1 and VEGFR-2, and focuses on the signaling pathways employed by VEGFR-1 and VEGFR-2 that regulate angiogenesis and their therapeutic potentials in angiogenesis-associated diseases.

Animals↗

PubMed1985

Nodular adenomatosis of iris pigment epithelium.

A 62-year-old man manifested multiple nodular growths in his left iris and unilateral glaucoma. Detailed clinical and pathologic studies showed that these lesions were adenomas derived from the spurs of Fuchs, Michel, and Grunert in the iris pigment epithelium. We suggest terming this newly described entity nodular adenomatosis of the iris pigment epithelium and propose a classification of primary neoplastic lesions of the iris.

Adenoma↗