PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Neovascularization, Pathologic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources

Molecular approaches to diagnosis and management of ovarian cancer.

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

Biomarkers, Tumor↗

Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1.

BACKGROUND: Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets. METHODS: Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data. RESULTS: VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1. CONCLUSION: Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.

Adenocarcinoma↗

Angiogenic activity of normal and pathologic human thyroid tissue.

Thyroid tissue was collected from 60 patients during operations for various thyroid conditions. The tissue's angiogenic capacity was assessed in a chick chorioallantoic membrane preparation. Angiogenic activity was observed in 22 (85%) of 26 solitary follicular neoplasms, in none of ten papillary carcinomas and in one of seven glands with Graves' disease (all pretreated with propranolol). Of 17 glands with euthyroid multinodular colloid goitre, three (18%) showed angiogenic activity. No angiogenic activity was detected in normal thyroid tissue from 26 patients. Angiogenic activity of diseased human thyroid does not seem to be a marker of thyroid malignancy.

Adult↗

[Hereditary retinal pathologies and AMD: new therapeutic perspectives].

This article summarizes our current knowledge on two types of retinal diseases: hereditary retinal degeneration and wet aged-related macular degeneration. Our understanding of retinal physiopathology in hereditary retinal degeneration and the successful experimental therapeutic results on animal models call for a new approach to these patients to prepare future clinical trials. Longitudinal follow-up of the functional alteration rhythm based on international standards and by expert centers is an essential prerequisite to including these patients in future clinical trials. Creating international databases that include data on follow-up using electrophysiological, psychophysical and morphological analyses would require standards defining how each of these procedures should be carried out. Furthermore, the relevance and value of the various examinations would then be evaluated in a longitudinal manner. The repeated use of these procedures in the various centers would bring to light any limitations these techniques may have for use in prospective studies. Continuous re-evaluation of these investigative techniques will therefore be necessary, a crucial factor in the preparation of multicenter clinical studies. The inclusion of patients phenotyped at different centers would require that certification procedures be set up for these centers. A great leap forward, clinical trials on new antiangiogenic approaches for the treatment of neovascular AMD are currently underway. The reasons for the switch between the neovascular and atrophic forms of AMD are as yet unknown, but these new approaches are based on the events that occur sequentially during the angiogenic response.

Clinical Trials as Topic↗

VEGFc and VEGFR3 expression in human thyroid pathologies.

In vertebrates, vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are major determinants of angiogenesis. In adults, the interaction between VEGFc and VEGFR3 (previously FLT4) is more specifically involved in the biology of lymphatics. Using PCR amplification of reverse-transcribed mRNA, we studied the expression of the VEGFR3 (including its short and long forms) and VEGFc genes in 38 samples of various human thyroid pathologies. VEGFR3 mRNA was detected in all samples of adenomas, nodular goiters and focal goitrogenic alterations; in all samples of thyroid tissue from patients with auto-immune diseases; and in some samples of adenocarcinomas. VEGFc mRNA was detected in most samples. We studied expression of the VEGFR3 and VEGFc proteins in thyroid tumors using appropriate antibodies. Co-expression of VEGFR3 and VEGFc was observed in most samples.

Adenocarcinoma↗

Intraorbital and periorbital tumors in children--value of ultrasound and color Doppler imaging in the differential diagnosis.

PURPOSE: To evaluate the role of ultrasonography (US) and color Doppler imaging (CDI) in the diagnosis of orbital tumors in children. DESIGN: Retrospective nonrandomized interventional case series. METHODS: This study included 42 children with intraorbital and periorbital tumors who were evaluated in our clinic. All children underwent a complete clinical evaluation as well as orbital US and CDI. The children then underwent operation or were followed up, based on the clinical diagnosis and the findings on the imaging modalities. RESULTS: The mean age of the patients at diagnosis was 22.5 months (range 2 weeks-14 years old). Eighteen patients (12 female and 6 male) were diagnosed with hemangioma based on the findings in US and CDI; 16 patients (9 female and 7 male) were diagnosed with dermoid, 5 patients (4 female and 1 male) with lymphangioma, 2 patients with rhabdomyosarcoma, and 1 patient with a subperiostal abscess. Twenty-two patients underwent operation, and the diagnosis was confirmed on pathology. Twenty patients did not undergo operation and continued to be followed up in the clinic (mean follow-up period 38.2 months). The disease course in all patients who did not undergo operation was consistent with the working diagnosis. CONCLUSION: Both US and CDI are useful modalities in the diagnosis of intraorbital and periorbital tumors in the pediatric age group.

Adolescent↗

Measuring tortuosity of the intracerebral vasculature from MRA images.

The clinical recognition of abnormal vascular tortuosity, or excessive bending, twisting, and winding, is important to the diagnosis of many diseases. Automated detection and quantitation of abnormal vascular tortuosity from three-dimensional (3-D) medical image data would, therefore, be of value. However, previous research has centered primarily upon two-dimensional (2-D) analysis of the special subset of vessels whose paths are normally close to straight. This report provides the first 3-D tortuosity analysis of clusters of vessels within the normally tortuous intracerebral circulation. We define three different clinical patterns of abnormal tortuosity. We extend into 3-D two tortuosity metrics previously reported as useful in analyzing 2-D images and describe a new metric that incorporates counts of minima of total curvature. We extract vessels from MRA data, map corresponding anatomical regions between sets of normal patients and patients with known pathology, and evaluate the three tortuosity metrics for ability to detect each type of abnormality within the region of interest. We conclude that the new tortuosity metric appears to be the most effective in detecting several types of abnormalities. However, one of the other metrics, based on a sum of curvature magnitudes, may be more effective in recognizing tightly coiled, "corkscrew" vessels associated with malignant tumors.

Brain↗

Effect of dietary energy restriction on vascular density during mammary carcinogenesis.

Inhibition of mammary carcinogenesis by dietary energy restriction is associated with a decrease in cell proliferation and the induction of apoptosis. Although changes in the metabolism of insulin-like growth factor I and glucocorticoids have been proposed to modulate these cellular processes, limitations in blood supply could induce similar effects. To investigate this possibility, female Sprague Dawley rats were given an injection of 1-methyl-1-nitrosourea and fed purified diets ad libitum or at 60% ad libitum intake, i.e., 40% dietary energy restriction. Premalignant mammary pathologies and mammary adenocarcinomas obtained from these rats were processed for vascular density analysis via CD-31 immunostaining. Vascular density, measured as vessels/unit area, of premalignant mammary pathologies and adenocarcinomas from dietary energy restriction rats was reduced 31 and 39%, respectively (P < 0.01). This effect, which was observed in a 50-microm wide band of tissue surrounding each pathology, was exerted on blood vessels > 25 microm2. Conversely, intratumoral vascular density was unaffected by dietary energy restriction. cDNA microarray and Western blot analyses of adenocarcinomas for evidence of dietary energy restriction-mediated effects on vascularization revealed that only the level of vascular endothelial growth factor receptor protein Flk-1 was significantly reduced (P < 0.001). It appears that dietary energy restriction imposes limitations in the supply of blood to developing pathologies, an effect that could directly inhibit the carcinogenic process. The vascular density data imply that dietary energy restriction inhibited the growth of endothelial cells but leave unresolved the question of whether dietary energy restriction had a specific effect on angiogenesis. The factors that account for the failure of dietary energy restriction to limit intratumoral vascularization are not obvious and merit additional investigation.

Animals↗

The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer.

Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29-70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at x 200 magnification. Median counts were correlated with clinical and pathological response using the Mann-Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5-8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference -0.5/hpf, 95% CI=-2.5-2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy.

Adult↗

Signal transduction pathways as targets for therapeutics.

Meeting information: AAAS 2001 Annual Meeting and Science Innovation Exposition, San Francisco, California, February 15 through 20, 2001. Science's STKE sponsored a symposium at the AAAS Annual Meeting in February 2001. Five speakers addressed the signaling pathways that are modified in wide-ranging pathologies including inflammation, impotence, diabetes, obesity, and cancer. The molecular targets of signaling pathways included cell surface molecules, such as the G protein-coupled receptors (GPCRs) and receptor tyrosine kinases, and intracellular signaling components, such as phosphodiesterases (PDEs) and components of the small guanosine triphosphatase (GTPase) Ras signaling pathway. Analysis of the therapeutic strategies to impinge on these various pathways provides insight into both the potential of signaling pathways as relevant drug targets and the possible pitfalls that make complex signaling networks unpredictably difficult targets for such manipulation.

Animals↗

[The effects of the expression of VEGF and KDR on the angiogenesis, growth and metastasis of hepatocellular carcinoma].

OBJECTIVE: To investigate the effects of VEGF (vascular endothelial growth factor) and KDR (kinase insert domain containing receptor) on the angiogenesis, growth and metastasis of hepatocellular carcinoma. METHODS: With the methods of immunohistochemistry and in situ hybridization, specimens from 45 HCC (hepatocellular carcinoma) patients, 21 cirrhotics, 8 normal livers patients were stained. Image analysis was followed, and the relationship between VEGF, KDR expression and the pathological characteristics of HCC was studied. RESULTS: VEGF was highly expressed in HCC and was correlated with the angiogenesis of HCC. The expression rate and the intensity of VEGF were correlated with the metastasis and capsule formation of HCC. KDR was expressed not only in vascular endothelial cells, but also in some HCC cells. CONCLUSIONS: VEGF may play an important role in the angiogenesis, metastasis, and capsule formation. The KDR expression in HCC cells may be a behavior of autocrine.

Carcinoma, Hepatocellular↗

Caveolin-I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma.

Extrahepatic bile duct carcinoma (EBDC) is a malignancy well known for its poor prognosis. Some clinicopathological prognostic markers have been proposed, but genetic factors have not been well investigated. We have examined expression patterns of caveolin-1, which has been shown to function as a tumour suppressor in vitro, in EBDC using immunohistochemistry. Normal tissues adjacent to the tumour cells did not show immunoreactivity for caveolin-1. A total of 22 of the 60-carcinoma tissue samples (36.7%) studied were positive for caveolin-1. Caveolin-1 immunostaining negatively correlated with the patient's age and pathological T factor (pT) in a statistically significant manner. Multivariate analysis using Cox's proportional hazards model identified caveolin-1 expression as an independent positive prognostic factor. Thus, our study suggests that caveolin-1 expression may be a useful prognostic marker for EBDC.

Adult↗

[Angiogenesis and its regulation].

Angiogenesis (formation of new blood vessels) is essential in embryonal development, female reproduction and wound repair. Under these physiological conditions, angiogenesis is highly regulated by the endogenous angiogenic factor and its inhibitor. However, angiogenic diseases such as rheumatoid arthritis, diabetic retinopathy, solid tumor, hemangioma and psoriasis are driven by persistent unregulated angiogenesis. The angiogenic process consists of such multi-steps as degradation of basement membrane, cell migration and proliferation, and tube formation following activation of vascular endothelial cells by stimulators appearing at the pathological site. Thus, for modulating the pathological conditions, it is most important to elucidate the angiogenic mechanism at the molecular level. It is not sufficiently clear yet as compared with the blood coagulation and hematopoietic systems. On the other hand, there have been advances in the study of new anticancer metastatic agents as a target of activated endothelial cells and they have been found to have promising substances. In this study, the angiogenic factor, its inhibitor, and then the anticancer effect of the angiogenic inhibitor, have been investigated from the standpoint of cancer therapy.

Angiogenesis Inducing Agents↗

Molecular diagnosis of tumor angiogenesis and anti-angiogenic cancer therapy.

Angiogenesis is regulated by the balance of pro-angiogenic factors and angiogenesis inhibitors, and the imbalance of these regulators is the cause of pathological angiogenesis, including tumor angiogenesis. Angiogenesis is required for tumor growth and metastasis, and thus constitutes an important target for the control of tumor progression. While the benefit of anti-angiogenic therapy is potentially profound, limitations have also been recognized by the results obtained thus far by clinical trials. Precise understanding of the process of angiogenesis should lead us to new regimens for more efficient anti-angiogenic therapy. This review focuses on our current understanding of the molecular mechanism of tumor angiogenic and the status of the anti-angiogenesis approach for cancer treatment.

Angiogenesis Inhibitors↗

Association of maspin expression with the malignancy grade and tumor vascularization in breast cancer tissues.

Maspin belongs to a tumor suppressing protein which is usually expressed highly in myoepithelial cells, and is significantly downregulated in breast cancer cells. We focused on identifying the correlation between maspin expression and the clinicopathological features of human breast cancer tissues using immunohistochemistry. There was a significant correlation in that maspin-positive tumor specimens showed a low pathological grade of malignancy, such as a lower infiltration of the tumor into the surrounding tissue and a downregulation of c-erbB2 expression. Moreover, maspin-positive cases showed a significant decrease in tumor vessels positively stained with anti-factor VIII-related antigen antibody. These results suggest that maspin production in myoepithelial cells could downregulate the malignant phenotype of breast cancer.

Biomarkers, Tumor↗

A fragment of human TrpRS as a potent antagonist of ocular angiogenesis.

Pathological angiogenesis contributes directly to profound loss of vision associated with many diseases of the eye. Recent work suggests that human tyrosyl- and tryptophanyl-tRNA synthetases (TrpRS) link protein synthesis to signal transduction pathways including angiogenesis. In this study, we show that a recombinant form of a COOH-terminal fragment of TrpRS is a potent antagonist of vascular endothelial growth factor-induced angiogenesis in a mouse model and of naturally occurring retinal angiogenesis in the neonatal mouse. The angiostatic activity is dose-dependent in both systems. The recombinant fragment is similar in size to one generated naturally by alternative splicing and can be produced by proteolysis of the full-length protein. In contrast, the full-length protein is inactive as an antagonist of angiogenesis. These results suggest that fragments of TrpRS, as naturally occurring and potentially nonimmunogenic anti-angiogenics, can be used for the treatment of neovascular eye diseases.

Alternative Splicing↗

The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications.

Besides its role as an essential regulator of physiologic and pathologic angiogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopoiesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome.

Animals↗

CXC chemokines in angiogenesis related to pulmonary fibrosis.

Angiogenesis, defined as the growth of new capillaries from preexisting vessels, is a pervasive biological phenomenon that is at the core of many physiologic and pathologic processes. An opposing balance of angiogenic and angiostatic factors regulates angiogenesis. Examples of physiologic processes that depend on angiogenesis include embryogenesis, wound repair, and the ovarian/menstrual cycle. In contrast, chronic inflammation associated with chronic fibroproliferative disorders as well as growth and metastasis of solid tumors are associated with aberrant angiogenesis. CXC chemokines comprise a unique cytokine family that contains members that exhibit on a structural/functional basis either angiogenic or angiostatic biological activity. In this review, we will discuss the role of CXC chemokines and angiogenesis in pulmonary fibrosis.

Chemokines, CXC↗