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Results for “Neovascularization, Pathologic”

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PubMed2004

Multidetector row CT of the pancreas.

Multidetector CT (MDCT) has gained a great role in clinical imaging practice in a short time. Its major advantages are faster image acquisition and improved z-axis resolution. In spite of the advent of other imaging modalities CT is still the gold standard for the evaluation of pancreatic pathology. In this article, a review of the utility of MDCT in pancreatic applications is given with emphasis on acquisition techniques tailored to contrast material pharmacokinetics to improve lesion detection and characterization.

Angiography↗

PubMed2000

Pathological angioarchitecture in lymph nodes: underlying histopathologic findings.

Pathologic changes of the intranodal angioarchitecture, as displayed by colour Doppler sonography, were used in recent studies to predict malignant infiltration of superficial lymph nodes. We searched for the underlying histopathologic findings in a prospective study including 100 lymph nodes in 86 patients. In the histopathologic specimens, we evaluated tumour infiltration, distribution of intranodal vessels, hilar structures, thickness of the capsule and tissue alterations (necrosis, sclerosis, lipo-/fibromatosis). Using the only prospectively tested classification, a pathologic angioarchitecture was described as displacement, aberrant course, avascular foci or subcapsular vessels. Testing these four criteria by multivariate regression analysis, the most important correlations were found between the following pairs of sonographic and histopathologic findings: displacement with perinodal tumour spread, aberrant vessels with intranodal sclerosis, avascular foci with intranodal necroses and subcapsular vessels with intranodal necroses. In conclusion, the criteria describing a pathologic angioarchitecture correlate with histopathologic findings that are frequently seen in malignant lymph nodes.

Adolescent↗

PubMed2006

Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro.

Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed no vascular defects during normal development or during neonatal oxygen-induced retinopathy. However, Cd151-null mice showed impaired pathologic angiogenesis in other in vivo assays (Matrigel plug, corneal micropocket, tumor implantation) and in the ex vivo aortic ring assay. Cd151-null mouse lung endothelial cells (MLECs) showed normal adhesion and proliferation, but marked alterations in vitro, in assays relevant to angiogenesis (migration, spreading, invasion, Matrigel contraction, tube and cable formation, spheroid sprouting). Consistent with these functional impairments, and with the close, preferential association of CD151 with laminin-binding integrins, Cd151-null MLECs also showed selective signaling defects, particularly on laminin substrate. Adhesion-dependent activation of PKB/c-Akt, e-NOS, Rac, and Cdc42 was diminished, but Raf, ERK, p38 MAP kinase, FAK, and Src were unaltered. In Cd151-null MLECs, connections were disrupted between laminin-binding integrins and at least 5 other proteins. In conclusion, CD151 modulates molecular organization of laminin-binding integrins, thereby supporting secondary (ie, after cell adhesion) functions of endothelial cells, which are needed for some types of pathologic angiogenesis in vivo. Selective effects of CD151 on pathologic angiogenesis make it a potentially useful target for anticancer therapy.

Animals↗

PubMed2003

Integrin alpha v beta 3 as a therapeutic target for blocking tumor-induced angiogenesis.

The integrin receptor alphavbeta3 has been shown to play a critical role in several distinct processes, such as angiogenesis, osteoclast-mediated bone resorption and tumor metastasis. Its expression is upregulated in newly synthesized blood vessels produced in response to a variety of tumors and purified angiogenic factors. Studies show that alphavbeta3 is a critical target downstream from perhaps all angiogcnic factors. Proof-of-principle that alphavbeta3 antagonists such as monoclonal antibodies and small molecules block angiogenesis and tumor growth has been obtained in several animal models. Many endogenous inhibitors of angiogenesis such as angiostatin, endostatin and tumstatin seem to work through the alphavbeta3 receptor further emphasizing the critical role of this receptor in angiogenesis. In addition, the alphavbeta3 receptor has been clearly implicated in several pathological processes such as rheumatoid arthritis, osteoporosis, and metastasis of prostate cancer to bone. Thus alphavbeta3 may prove to be an important target for pharmacological intervention in more than one clinical setting.

Angiogenesis Inhibitors↗

PubMed1995

Angiogenesis-directed implantation of genetically modified endothelial cells in mice.

By virtue of their location within blood vessels and their ability to express foreign genes, endothelial cells are attractive vehicles for the delivery of therapeutic molecules in vivo. We wished to determine whether i.v.-injected, genetically modified endothelial cells can become incorporated into sites of active angiogenesis in vivo. To do so, we studied the fate of i.v.-injected, lacZ-expressing human umbilical vein endothelial cells in athymic nude mice bearing lethally irradiated NIH 3T3 murine fibroblast cells transfected with a sp-hst/KS3:fibroblast growth factor-1 chimera that forces the secretion of the angiogenic protein, fibroblast growth factor-1. Following i.v. injection, lacZ-labeled human umbilical vein endothelial cells accumulated at sites of fibroblast growth factor-1-induced angiogenesis, persisting for at least 4 weeks. These results suggest that i.v.-administered, genetically modified endothelial cells can migrate into and survive within an angiogenic site. This strategy may be useful for delivery of therapeutic molecules to sites of pathological angiogenesis during tumor metastasis.

3T3 Cells↗

PubMed2003

Angiogenesis in hypersensitivity pneumonitis.

Angiogenesis is an essential process required for growth and tissue repair after injury, but it may also contribute to the pathology of a number of human disorders including neoplasias, atherosclerosis and inflammatory diseases. Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide upregulated by many cytokines and endothelium shear stresses. Lung is a highly vascular tissue with finely organized and regulated microvascular beds, and its inflammation may lead to dysregulated angiogenesis. Hypersensitivity pneumonitis (HP) is a lung disorder characterized by chronic lymphocytic inflammation and endothelial damage. However, neovascularization has not been previously explored. In this study, we examined the expression and localization of VEGF in 38 patients with HP and 14 healthy control subjects (CS). VEGF levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, and cellular lung localization was determined by immunohistochemistry. In addition, VEGF expression was analyzed in lung tissue by RT-PCR. Our results showed sera levels significantly increased in HP patients compared with CS (209.3 +/- 189.3 vs. 55.3 +/- 31.4 pg/ml; p = 0.004). By contrast, BALF levels of VEGF were significantly decreased in HP patients compared with CS (35.3 +/- 51.5 pg/ml vs. 185.1 +/- 191.4 pg/ml; p < 0.001). VEGF was primary expressed by epithelial cells, smooth muscle cells, and interstitial macrophages in HP tissue. Flt-1 and Flk-1 receptors were highly expressed by endothelial cells from medium and small vessels in HP tissue. By RT-PCR the VEGF RNA was increased compared with those in normal lung. Our results suggest that abnormal expression of VEGF may contribute to impair the lung repair in HP.

Alveolitis, Extrinsic Allergic↗

PubMed2006

Sonographic features of nonpalpable breast cancer: a study based on ultrasound-guided wire-localized surgical biopsies.

The purpose of this study is to investigate the correlation between surgicopathological findings and ultrasonic images of nonpalpable breast lesions. The study was composed of 220 nonpalpable breast lesions from 193 patients. The breast lesions were classified into soft tissue type (185 lesions) and calcification type (35 lesions). Of the 220 lesions, 62 (28%) were malignant. For soft tissue type lesions, the sonographic features of sound attenuation (p < 0.001) and irregular border (p < 0.001) were significantly associated with the malignant diagnosis. For soft tissue-type and calcification-type lesions, the presence of increased vascularity (p < 0.001) or calcification (p < 0.001) was significantly associated with the malignant diagnosis. Of the 164 breast lesions with corresponding mammograms, 37 of 74 mammographically identifiable lesions were pathologically malignant, as compared with 16 of 90 lesions with negative mammograms (p < 0.001). In our study, the more sensitive sonographic features for predicting malignancy were irregular border and increased vascularity (sensitivity 88% and 82%, respectively), whereas the features of sound attenuation and presence of calcifications were more specific (specificity 88% and 80%, respectively). In conclusion, ultrasound-guided wire localization of breast lesions is not only useful in assisting surgical biopsy, but the sonographic findings obtained by this procedure correlate with pathologic diagnosis.

Adolescent↗

PubMed2004

Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation.

Preinvasive mammary pathologies in humans and rat chemical carcinogenesis model systems have an increased microvascular density relative to normal tissue. This suggests the possibility of preventing invasive breast cancer by inhibiting angiogenesis. Vascular endothelial cell growth factor (VEGF) is a potent angiogenic growth factor, commonly involved in tumor-induced angiogenesis. Here, we show that both VEGF and VEGFR2 expression increase with histological progression to invasive disease in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model. Other VEGF receptors, VEGFR1, neuropilin 1 and neuropilin 2, are constitutively expressed throughout progression. To examine whether VEGF signaling is functionally relevant to tumor-induced endothelial tubule formation in vitro and for tumor formation in vivo, we utilized the VEGFR2 inhibitor, ZD6474. In vitro endothelial cell tubulogenesis induced by isolated mammary organoids or carcinoma in situ from DMBA-treated rats is inhibited by ZD6474, in a dose-dependent fashion. The administration of ZD6474 to DMBA-treated rats inhibits the formation of atypical ductal hyperplasia and carcinoma in situ by greater than 95% (P < 0.05), when administered 1 week or 6 weeks post-DMBA initiation. Invasive disease was absent in all ZD6474 cohorts. These data support the hypothesis that progression of DMBA-induced preinvasive mammary pathologies to palpable disease requires angiogenesis via a VEGF-dependent mechanism.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Vascular endothelial growth factor in breast cancer: biologic and therapeutic aspects.

Angiogenesis, or new blood vessel formation, is known to be an important part of the malignant phenotype in most cancers, including breast cancer. Recent years have seen the discovery of many regulators of the angiogenic process. Foremost among these is vascular endothelial growth factor (VEGF), the ligand for a family of specific transmembrane receptors that regulate the angiogenic process. This article describes the role of VEGF and its receptors in angiogenesis (both physiologic and pathologic), and describes efforts to target VEGF and its receptor. It discusses the outcome of some early trials involving VEGF-targeting agents, and reviews future therapeutic trials involving VEGF in breast cancer.

Angiogenesis Inhibitors↗

PubMed2004

Chronic systemic hypoxia causes intra-retinal angiogenesis.

Retinal hypoxia occurs in many conditions that cause vascular disease in the eye and is an important stimulus to new vessel formation. However, the adult retina can also become hypoxic when there is systemic hypoxaemia such as occurs in chronic lung diseases, congenital cardiac disease and residence at high altitude. Little is known about the adaptive responses of the retinal vasculature in such circumstances. Previous research in the retinopathy of prematurity model may not apply to the adult tissue given the different mechanisms controlling angiogenesis in developing and mature circulations. We tested the hypothesis that chronic systemic hypoxia leads to angiogenesis in the adult retinal circulation, in the absence of pre-existing vascular disease. Adult male Sprague-Dawley rats (n=9) were exposed to a fraction of inspired oxygen of 0.10 for 2 weeks while control animals (n=10) were exposed to room air. Stereological techniques were used to quantify the vascular volume, endothelial surface area and the total number of branch points of all blood vessels in the superficial retinal vascular plexus. The mean volume and endothelial surface area of these vessels were significantly greater in the hypoxic than in the control group. The mean number of blood vessel branch points was also significantly greater in the hypoxic group. Our findings demonstrate that chronic systemic hypoxia, in the absence of other pathological processes, causes angiogenesis in the adult rat retina and provide an in vivo model for investigating this important process in the adult retina, in particular pathways specific to this tissue.

Animals↗

PubMed1997

Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.

Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred after disruption of the Tie2 ligand. These findings indicate that the Tie2/Tie2 ligand pathway plays important roles during development of the embryonic vasculature. To determine whether the Tie2 pathway was involved in pathologic angiogenesis in adult tissues, a soluble form of the extracellular domain of murine Tie2 (ExTek.6His) was developed and used as a Tie2 inhibitor. After a single application of the ExTek.6His protein into a rat cutaneous window chamber, growth of a mammary tumor inside the chamber was reduced by > 75% (P < 0.005), and tumor vascular length density was reduced by 40% when compared with control-treated tumors (P < 0.01). In the rat cornea, ExTek.6His blocked angiogenesis stimulated by tumor cell conditioned media. ExTek.6His protein did not affect the viability of cultured tumor cells, indicating that the antitumor effect of ExTek.6His was due to the inhibition of tumor angiogenesis. These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases.

Animals↗

PubMed2005

Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection.

Chronic inflammation in the airways is associated with dramatic architectural changes in the walls of the airways and in the vasculature they contain. In this study, we show that the adaptive immune system is essential for airway remodeling that occurs in mice that are chronically infected with the respiratory pathogen Mycoplasma pulmonis. Angiogenesis, lymphangiogenesis, and epithelial remodeling were greatly reduced in mice that lacked B cells. Substantiating a role for Ab and airway immune complexes, we found that the transfer of immune serum to B cell-deficient mice could reconstitute pathogen-induced angiogenesis. Inflammatory cells recruited to the infected airways were activated by the humoral response, and this activation correlated with the induction of genes for remodeling factors such as vascular endothelial growth factor-D. The results reveal a novel pathway whereby T cell-dependent humoral immunity to a persistent airway infection can induce inflammation-dependent angiogenesis, lymphangiogenesis, and chronic airway pathology.

Animals↗

PubMed2002

Effects of betamethasone, sulindac and quinacrine drugs on the inflammatory neoangiogenesis response induced by polyurethane sponge implanted in mouse.

In this study, we showed the effect of the betamethasone, sulindac and quinacrine alone or combined, on the inflammatory angiogenesis promoted by polyurethane sponge on mice. The main finding reported here is that the formation of new blood vessels was strongly inhibited by low concentration of betamethasone, sulindac or quinacrine, whether alone or in combination. It is known that steroidal anti-inflammatory drugs inhibit the enzymes required for the production of prostaglandins through a nuclear glucocorticoid receptor (GR) mediated mechanism. This mechanism may occur in endothelial cells as well. Considering that activity of cyclo-oxigenases 1 and 2 is inhibited by sulindac, and that these enzymes are located in the stromal tissue, we propose that the anti-angiogenic effect of these agents may occur via inhibition of both COX isoforms. On the other hand, quinacrine inhibited PLA2 activity, and we propose here that the anti-angiogenic effect occurs via inhibition of the enzyme PLA2. The potentiated effect of the association of betamethasone, sulindac and quinacrine may have some therapeutic benefit in the control of pathological angiogenesis. Further studies are required to validate these propositions.

Animals↗

PubMed2005

[Pathologic change of elastic fibers with difference of microvessel density and expression of angiogenesis-related proteins in internal hemorrhoid tissues].

OBJECTIVE: To investigate the pathological variations in internal hemorrhoid and evaluate the expression of nitric- oxide synthase(NOS),vascular endothelial growth factor(VEGF),matrix metalloproteinase- 2(MMP2) and MMP9. METHODS: Normal anal cushion and internal hemorrhoids tissue samples were obtained from 24 patients with iii degree hemorrhoids after procedure for prolapse and hemorrhoids(PPH) procedure. The expression of NOS, VEGF, MMP2, MMP9 and CD34 were detected by immunohistochemical staining; the microvessel density (MVD) was counted by anti- CD34 antibody; the elastic fibers were detected by orcein staining. RESULTS: There were statistically significant differences in the expression of MVD, VEGF, MMP9 between internal hemorrhoid tissue and normal anal cushions(P< 0.05). iNOS was significantly increased in hemorrhoid tissue, but no significant difference between normal anal cushions and hemorrhoid tissue. Morphological abnormalities such as breaking, distortion, mortality, hyaline degeneration were found in elastic fibers of internal hemorrhoid tissue, but not in normal anal cushions. CONCLUSION: Angiogenesis is evident in hemorrhoid tissue, suggesting the possible mechanism in the pathogenesis of hemorrhoids. The direct degeneration effect of MMP9 on supporting structure elastic fibers in anal cushion is another important mechanism. The high expression of iNOS suggests the inflammatory factors involve in the pathogenesis of hemorrhoids, and NO may be involve in pathological effect on hemorrhoids.

Adult↗

PubMedDate not supplied

Biliary cystadenoma and cystadenocarcinoma: two rare cystic liver lesions.

A case of hepatobiliary cystadenoma with mesenchymal stroma and a case of biliary cystadenocarcinoma are presented. Hepatobiliary cystadenoma and cystadenocarcinoma are rare liver lesions that are difficult to diagnose preoperatively. Regardless of the diagnostic modalities used these two pathologies cannot be differentiated with accuracy. The preoperative diagnosis of biliary cystadenoma and cystadenocarcinoma was suggested due to the radiological detection of vascularity in the septa and the invasion of the thoracoabdominal wall. The surgeon was informed in both of the cases. Pathologic examination confirmed the diagnosis in both of our patients. The radiological features of these pathologies are discussed in detail together with a brief review of the literature.

Abdominal Wall↗

PubMed2005

Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in vivo. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high affinity VEGF receptors. VEGF plays an essential role in developmental angiogenesis and is important also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with VEGF inhibitors in a variety of malignancies are ongoing. Recently, a humanized anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the FDA as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.

Angiogenesis Inhibitors↗

PubMed1994

The role of tissue inhibitor of metalloproteinase-1 in specific aspects of cancer progression and reproduction.

Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of the multi member family of matrix metalloproteinases (MMPs). Since MMP function is fundamental to events that require tissue remodelling, TIMPs regulate normal biological processes by inhibiting MMPs, and are of importance in pathological conditions. In this chapter we review evidence for the suppressive role of TIMP-1 in the malignant progression of cancer and of its regulatory function in controlling invasion during blastocyst implantation and development.

Cell Division↗

PubMed2006

The host's genetic background determines the extent of angiogenesis induced by schistosome egg antigens.

Schistosomiasis is characterised by periovular granuloma formation within the portal tract and presinusoidal venules. As inflammation wanes, continued attempts to wall off and repair hepatic injury, lead to the development of extensive fibrosis. The codependence of chronic inflammation and angiogenesis is a well-known phenomenon. Neovascularisation is a complex process of endothelial cell proliferation and remodelling of the extracellular matrix. Previous studies demonstrated the ability of schistosome soluble egg antigens (SEAs) to stimulate endothelial cell activation in vitro. In the present study, we investigated the angiogenic potential of SEA in Swiss and BALb/c mice, after infection with Schistosoma mansoni or S. haematobium and by implanting SEA-coated beads into the murine liver. Anti-CD34 and anti-Ki-67 immunohistochemical stainings demonstrated newly formed blood vessels within and at the periphery of the granulomas. However, in one third of the granulomas the pre-existing portal stroma was not destroyed by the granulomatous inflammation, angiogenesis was minimal or absent and further growth of the granuloma was prevented. In C57BL/6J and C3H/HeN inbred mice, this polarisation was even more pronounced. In 91% of the granulomas in C57BL6/J mice the portal stroma was preserved. These mice had significantly smaller granulomas, less fibrosis and less mortality as compared to the high pathology C3H/HeN mice, where 87% of the granulomas were of the angiogenic type with destruction of the pre-existing stroma, leading to more severe chronic pathology. Thus, host's genetic mechanisms regulating the degree of angiogenesis and fibrosis, determine the severity of schistosome-induced pathology.

Animals↗