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Results for “Neovascularization, Pathologic”

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PubMed2005

Interleukin 8 in human hepatocellular carcinoma correlates with cancer cell invasion of vessels but not with tumor angiogenesis.

BACKGROUND: Angiogenic factor seems necessary for the development of hepatocellular carcinoma (HCC), which is a hypervascular malignancy. This study examined the expression of interleukin (IL)-8, a potent angiogenic factor, in HCC samples. METHODS: We measured IL-8 expression by using reverse transcriptase-polymerase chain reaction in clinical HCC tissues from 45 patients who underwent surgical resection. We then assessed correlations between IL-8 expression and microvessel growth or clinicopathologic factors. We also elucidated the in vitro effect of IL-8 on HepG2 development by using fluorometric assays of proliferation, chemotaxis, and invasion. RESULTS: The expression of IL-8 did not significantly correlate with the microvessel count in HCC tissues, but the incidence of microscopic vessel invasion was significantly higher in IL-8-positive than in IL-8-negative tissues. Thus, more IL-8 was expressed in HCCs at pathologic stage III/IV than in those at stage I/II. Assays in vitro showed that IL-8 stimulates HepG2 chemotactic and invasive activities rather than cell proliferation. CONCLUSIONS: The expression of IL-8 in human HCC has more relevance to metastatic potential, such as vessel invasion, than to angiogenesis or cell proliferation.

Adult↗

PubMed2003

Prognostic and predictive indicators in operable breast cancer.

Because of its biological heterogeneity and wide spectrum of responsiveness to different treatments, breast cancer is a complex disease of difficult clinical management. Over the past several years, knowledge of the molecular mechanisms regulating normal and aberrant cell growth leading to cancer has been enhanced. These advances have enabled the identification of an increasing number of surrogate biomarkers, which have been correlated with prognosis or used as predictors of response to specific treatments. Axillary nodal status, age, tumor size, pathologic grade, and hormone receptor status are the established prognostic and/or predictive factors for selection of adjuvant treatments. The role of new biomarkers, such as p53, HER2/neu, angiogenesis, and the proliferation index value, is promising; however, the clinical value of their determination must be provided by prospective clinical studies.

Breast Neoplasms↗

PubMed1999

[Vascular remodeling and angiotensin II].

Numerous pharmacological approaches have failed to modify the high incidence of restenosis after balloon coronary angioplasty. This inability to alter the restenosis process was caused in part by our incomplete understanding of its pathology. Neointimal formation and geometric remodeling cause the restenosis after angioplasty. The development of restenosis involves vascular smooth muscle cells (VSMCs) migration and proliferation. Angiotensin II has been shown to stimulate the growth of VSMCs via an action on the angiotensin II AT1 receptor subtype. Angiotensin II AT1 receptor antagonists can block the angiotensin II-induced these actions. Angiotensin II AT1 receptor antagonists may block the restenosis after balloon coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2002

Contrast-enhanced dynamic computed tomography for the evaluation of tumor angiogenesis in patients with lung carcinoma.

BACKGROUND: The objective of this study was to investigate the role of contrast-enhanced dynamic computed tomography (CT) in the evaluation of tumor angiogenesis in patients with lung carcinoma and to assess its importance in predicting tumor size and lymph node involvement. METHODS: Dynamic CT scans were evaluated retrospectively in 130 patients with primary lung carcinoma who did not have distant metastasis and who underwent surgical resection with mediastinal lymph node dissection. Histopathologic findings of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) were correlated with the maximum attenuation values of time-attenuation curves (MAV) on dynamic CT scans. RESULTS: The MAV in VEGF positive tumors was greater compared with the MAV in VEGF negative tumors (66.1 +/- 4.6 vs. 30.9 +/- 2.7, respectively; P < 0.0001). An association was found between the MAV in VEGF positive tumors and MVD (correlation coefficient = 0.650; P < 0.0001). No difference was found in tumor size with pathologic confirmation and the MAV, VEGF expression, or MVD. The MAV, VEGF expression, and MVD in lung tumors with lymph node involvement were greater compared with the same values in lung tumors without lymph node involvement. CONCLUSIONS: The MAV of dynamic CT may be a predictor of tumor angiogenesis in patients with lung carcinoma and lymph node involvement.

Adult↗

PubMed1998

Dysplastic nodules in cirrhotic liver: arterial phase enhancement at CT and MR imaging--a case report.

In a 65-year-old woman with cirrhosis, biphasic helical computed tomography (CT) and multiphase gadolinium-enhanced magnetic resonance (MR) imaging depicted 11 hepatic nodules that enhanced homogeneously during the hepatic arterial phase. At pathologic examination, all lesions were dysplastic nodules with unpaired hepatic arteries within. Hepatic arterial phase enhancement of cirrhotic nodules at CT and MR imaging is not diagnostic of hepatocellular carcinoma but may occur in dysplastic nodules. Results of a single biopsy yielding hepatocellular carcinoma may not be applicable to other nodules that enhance similarly.

Aged↗

PubMed2000

Clinicopathologic study of Castleman's disease in Korea.

Castleman's disease represents an atypical lymphoproliferative disorder, infrequently associated with various immunologic abnormalities or subsequent development of malignancy such as Kaposi sarcoma, malignant lymphoma and plasmacytoma. Its clinicopathologic features depend on various etiologic factors such as Kaposi sarcoma herpesvirus (KSHV), oversecretion of IL-6, adhesion molecule and follicular dendritic cell dysplasia, etc. To investigate the relationship of Castleman's disease (CD) and the above factors, we reviewed 22 cases of CD. Four cases of KSHV positive CD were detected, all multicentric, plasma cell type, and these cases displayed prominent vascular proliferation, characteristic 'Kaposi-like lesion'. IL-6 and CD54 positive mononuclear cells were scattered in interfollicular areas of KSHV positive cases. Follicular dendritic cell hyperplasia, vascular proliferation, expression of IL-6 and CD54 did not show any significant difference between solitary vs multicentric type, and plasma cell type vs hyaline vascular type. Our study suggests that KSHV positive CD reveals unique pathologic features, and the probable relationship of KSHV and IL-6 and CD54 is discussed.

Adolescent↗

PubMedDate not supplied

Ligand-targeted liposomes directed against pathological vasculature.

The development of liposomes targeted to angiogenic endothelial cells offers exciting prospects for intervention in cancer and inflammation. Several proteins are (strongly) over-expressed on angiogenic endothelial cells as compared to the quiescent endothelium, and could potentially serve as targets for site-specific drug delivery. In this contribution particular attention is given to the design of targeted long-circulating liposomes directed against the alpha v beta 3-integrin protein.

Cells, Cultured↗

PubMed1999

Tumor angiogenesis and recurrence in stage I non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis appears to relate to recurrence after an operation as a route for distant metastasis. We assessed the association of vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density (MD) with recurrence in primary lung cancer. METHODS: Samples were randomly obtained from 104 stage I lung cancer patients who underwent curative operations (43 recurrent, 61 nonrecurrent patients). Microvessels were highlighted by staining endothelial cells for factor VIII and VEGF antigen was detected using a polyclonal antibody. RESULTS: VEGF antigen was detected in large amounts in both recurrent (100%) and nonrecurrent tumors (73.8%). The percentages of patients with the strongest VEGF stain (more than 50% of staining area in tumor cells) were 46.5% in tumors with recurrence and 11.5% in tumors without recurrence. The mean MD in recurrent and nonrecurrent tumors were 18.2+/-10.5 and 8.5+/-5.0, respectively, resulting in a significantly greater value in tumors with recurrence (p<0.0001). Although there were no significant differences in mean MD according to pathological types, in adenocarcinoma and adenosquamous carcinoma, the mean value in the recurrent group was significantly greater than that in the nonrecurrent one. CONCLUSIONS: An evaluation of VEGF expression and MD in tumors may contribute to the estimation of the risk of recurrence of non-small cell lung cancer in early stages.

Adult↗

PubMed1987

[Endothelium, angiogenesis and metastasis].

The turnover of endothelium in a normal adult male is very low. Angiogenesis, the formation of new blood vessels, involves a high turnover of endothelial cells. It takes place during embryogenesis, ovulation and many pathological conditions, e.g. tumor growth. Soluble polypeptide growth factors for endothelial cells have been biochemically characterized. They are able to induce angiogenesis in vivo. Inhibitors of angiogenesis can inhibit tumor vascularization and the growth of solid tumors in mice. Tumor metastasis involves the migration of malignant tumor cells through endothelial cells. The organ and tissue specificity of these and other invasive migrations through vascular endothelium may be related to the heterogeneity and organ specificity of endothelial cells.

Animals↗

PubMed2006

Short and long-term effects of hVEGF-A(165) in Cre-activated transgenic mice.

We have generated a transgenic mouse where hVEGF-A(165) expression has been silenced with loxP-STOP fragment, and we used this model to study the effects of hVEGF-A(165) over-expression in mice after systemic adenovirus mediated Cre-gene transfer. Unlike previous conventional transgenic models, this model leads to the expression of hVEGF-A(165) in only a low number of cells in the target tissues in adult mice. Levels of hVEGF-A(165) expression were moderate and morphological changes were found mainly in the liver, showing typical signs of active angiogenesis. Most mice were healthy without any major consequences up to 18 months after the activation of hVEGF-A(165) expression. However, one mouse with a high plasma hVEGF-A(165) level died spontaneously because of bleeding into abdominal cavity and having liver hemangioma, haemorrhagic paratubarian cystic lesions and spleen peliosis. Also, two mice developed malignant tumors (hepatocellular carcinoma and lung adenocarcinoma), which were not seen in control mice. We conclude that long-term uncontrolled hVEGF-A(165) expression in only a limited number of target cells in adult mice can be associated with pathological changes, including possible formation of malignant tumors and uncontrolled bleeding in target tissues. These findings have implications for the design of long-term clinical trials using hVEGF-A(165) gene and protein.

Adenoviridae↗

PubMed2004

[The expression of matrix metalloproteinase-2 and -9 in cervical cancer and a study of their relationship].

OBJECTIVE: To detect the expressions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in cervical cancer and their correlation with clinicopathologic features. METHODS: With the use of specific monoclonal antibody to human MMP-2 and MMP-9, the formalin-fixed and paraffin-embedded specimens of 62 invasive carcinomas of cervix uteri, 5 carcinomas in situ, 10 normal cervical epithelia and 10 lymph node metastases were detected by immunohistochemical method. RESULTS: MMP-2 and MMP-9 protein expressions in tumor and peritumoral stromal cells were enhanced in invasive carcinoma, compared to those in carcinoma in situ and controls (P < 0.05). There was a low correlation between MMP-2 and MMP-9 (r = 0.34, P < 0.01); the expression level of MMP-9 was higher than MMP-2. The protein expressions of MMP-2 and MMP-9 did not correlate with tumor stage, histological grade or pathological subtype. MMP-9 was correlated with lymph node metastasis and lymphovascular space invasion. CONCLUSION: The over-expression of matrix metalloproteinase-2 and -9 was correlated with invasive behaviour of cervical cancer, MMP-9 was significantly correlated with the lymph node metastasis, it might become a useful prognostic indicator for early cervical cancer.

Adult↗

PubMed2004

Novel technologies and recent advances in metastasis research.

In this review we have attempted to summarize some of the recent developments in using novel technologies to unravel the molecular mechanisms of tumor progression, in particular the formation of tumor metastasis. In order to push forward the frontiers in cancer research, it is obvious that several fields have to be further developed and interconnected: (1) clinical, epidemiological and pathological studies which mainly use innovative technologies, including microarray technology and nanotechnology to determine as many parameters as possible, (2) the development of improved and suitable bioassays and better animal models and (3) the use of novel computation and bioinformatics methods to sample and integrate the exponentially growing sets of data coming from such investigations. Fashionable as scientists are, this new endeavor may be called systems biology.

Animals↗

PubMed2002

Visualization of microvascularity in glioblastoma multiforme with 8-T high-spatial-resolution MR imaging.

We used 8-T high-spatial-resolution gradient-echo MR imaging to directly visualize microvascularity in pathologically proved glioblastoma multiforme. Images were compared with 1.5-T high-spatial-resolution fast spin-echo T2-weighted images and digital subtraction angiograms. Preliminary data indicate that 8-T high-spatial-resolution MR imaging may enable the identification of areas of abnormal microvascularity in glioblastoma multiforme that are not visible with other routine clinical techniques.

Adult↗

PubMed2005

Hepatoma-derived growth factor as a prognostic marker in completely resected non-small-cell lung cancer.

Hepatoma-derived growth factor (HDGF), unrelated to hepatocyte growth factor, is a heparin-binding protein originally purified from human hepatoma HuH-7 cells. HDGF exhibits mitogenic activities for certain hepatoma cells, fibroblasts and vascular smooth muscle cells, and angiogenic activities through nuclear targeting. Recently, HDGF was found to be a mitogen for lung epithelial cells in vitro and in vivo. This suggests that HDGF may play a critical role in the development and progression of lung cancer. We investigated, immunohistochemically, the relationship between HDGF expression and clinicopathological variables, and the prognostic significance of HDGF in 102 patients with completely resected non-small-cell lung cancer (NSCLC: 70 adenocarcinomas and 32 squamous cell carcinomas). To address the mechanism of action of HDGF, we evaluated the contribution of HDGF to tumor cell proliferation and intratumor angiogenesis using anti-Ki-67 and anti-CD31 antibodies, respectively. HDGF expression was strongly detected in the nucleus of cancer cells; the HDGF-labeling index (LI) was 20-95% (median 64.5%). There was no significant association between HDGF-expression level and clinicopathological variables. Patients with NSCLC showing a high HDGF-LI (> or =65%) had significantly worse overall and disease-free survivals than those with NSCLC showing a low HDGF-LI. Multivariate analysis revealed that HDGF is a significant independent prognostic factor, more powerful than pathological stage. Moreover, HDGF expression correlated with Ki-67-LI and intratumor microvessel density. We consider HDGF as a useful prognostic marker for patients with completely resected NSCLC and it may play a critical role in the pathobiology of lung cancer through its mitogenic and angiogenic activities.

Adenocarcinoma↗

PubMed1985

Pathologic features of senile macular degeneration.

Senile macular degeneration (SMD) has several morphologic forms that may exist singly or in various combinations. Patients with drusen are at an increased risk to develop SMD. Types of drusen that have been recognized clinically and histopathologically include hard or nodular, soft, glistening or calcified, and diffuse. Hard drusen are probably a consequence of extrusion of material from one or a cluster of retinal pigment epithelial (RPE) cells. Soft drusen are a sign of more widespread disease of the RPE, develop in eyes with hard drusen, and represent small areas of serous detachment of the RPE and the thickened inner aspect of Bruch's membrane. RPE areolar atrophy can occur in the setting of hard and soft drusen and in larger RPE detachments. From the morphologic point of view, we propose that the process leading to disciform scar formation in SMD begins with thickening of the inner aspect of Bruch's membrane due to production of abnormal basement membrane by the RPE. This thickened area is weakly attached and allows the development of localized detachments (soft drusen). These localized detachments become confluent into large detachments of the RPE. Choroidal neovascularization occurs in association with diffuse and soft drusen and larger serous RPE detachments. Bleeding from neovascular tissue leads to disciform scar formation.

Atrophy↗

PubMed2002

Cyclooxygenase, lipoxygenase and tumor angiogenesis.

Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways generates various biologically active lipids that play important roles in inflammation, thrombosis and tumor progression. Angiogenesis, the formation of new capillary vessels from preexisting ones, underpins a number of physiological processes and participates in the development of several pathological conditions such as arthritis, cancer and various eye diseases. The formation of new capillary vessels is a multistep process that involves endothelial cell proliferation, migration and tube formation. In the present review, we survey the literature on the regulation of angiogenesis by arachidonate metabolites, especially those from the COX and 12-LOX pathways in the context of tumor growth, and put forward some unanswered but important questions for future studies.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.

The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies). The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P = .03). Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series (P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80). These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to carry out therapeutic protocol planning, which may be further enhanced by the adoption of the more recent antiangiogenic molecules.

Adenocarcinoma↗

PubMed2002

Recent advances in cancer research: mouse models of tumorigenesis.

Over the past 20 years, cancer research has gained major insights into the complexity of tumor development, in particular into the molecular mechanisms that underlie the progressive transformation of normal cells into highly malignant derivatives. It is estimated that the transformation of a normal cell to a malignant tumor cell is dependent upon a small number of genetic alterations, estimated to be within the range of four to seven rate-limiting events. Critical events in the evolution of neoplastic disease include the loss of proliferative control, the failure to undergo programmed cell death (apoptosis), the onset of neoangiogenesis, tissue remodeling, invasion of tumor cells into surrounding tissue and, finally, metastatic dissemination of tumor cells to distant organs. In patients, the molecular analysis of these multiple steps is hampered by the unavailability of tumor biopsies from all tumor stages. In contrast, mouse models of tumorigenesis allow the reproducible isolation of all tumor stages, including normal tissue, which are then amenable to pathological, genetic and biochemical analyses and, hence, have been instrumental in investigating cancer-related genes and their role in carcinogenesis. In this review, we discuss mouse tumor models that have contributed substantially to the identification and characterization of novel tumor pathways. In particular, we focus on transgenic and knockout mouse models that closely mimic human cancer and thus can be used as model systems for cancer research.

Animals↗