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Results for “Neovascularization, Pathologic”

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PubMedDate not supplied

[Prognostic significance of tumor-induced angiogenesis in colorectal carcinoma].

INTRODUCTION: Tumor-induced angiogenesis is a central pathogenic step in the process of tumor growth, invasion and metastasis. The aim of this study was to analyze the quantitative expression of angiogenesis in colorectal carcinoma and to determine if and how angiogenesis correlates with other clinicopathologic factors and prognosis. MATERIAL AND METHODS: This study included 40 patients who underwent curative resection of colorectal cancer at the Department of Surgery of the Senta General Hospital with complete 5 years follow-up or till death. Microvessels were identified immunohistochemically, using monoclonal CD31 antibodies. The microvessel count was assessed by means of stereology with test grid M42, as well as vascular surface density in the stromal volume at the invasive front of colorectal cancer. RESULTS: Tumor-induced angiogenesis count of colorectal carcinomas statistically significantly correlated with stage of disease and histologic tumor grade. There was no significant correlation between intratumoral microvessel density and sex and age of patients, localization and histologic tumor type. Five-year survival rate in patients with hypervascular colorectal tumors was statistically significantly lower than in patients with hypovascular tumors. Thus, microvessel density in colorectal cancer is an independent prognostic factor, but its significance is less than the importance concerning stage of disease and histologic grade of tumor. CONCLUSIONS: Intratumoral microvessel density quantification in histologic specimens of colorectal carcinoma reflects the biological malignant potential of tumors and may be a useful additional predictive marker. Assessment of intratumoral microvessel count might be used for determining the pathologic stage when adjuvant therapy is concerned. Microvessel density in tumor specimens is valuable in stratifying patients in planning appropriate adjuvant and antiangiogenic therapy after surgery.

Adult↗

PubMed2002

Biomarkers for breast cancer.

Molecular biomarkers for breast cancer are of several types. Risk biomarkers are those associated with increased cancer risk and include mammographic abnormalities, proliferative breast disease with or without atypia, family clustering and inherited germ-line abnormalities. Surrogate endpoint biomarkers are tissue, cellular or molecular alterations that occur between cancer initiation and progression. These biomarkers are utilized as endpoints in short-term chemoprevention trials. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki-67 and proliferating cell nuclear antigen (PCNA); ER and PR overexpression; markers of oncogene overexpression such as c-erbB-2, TGF-a and EGFr; indicators of apoptotic imbalance including overexpression of bcl-2 and an increased bax/bcl-2 ratio; markers of disordered cell signaling such as p53 nuclear protein accumulation; alteration of differentiation signals such as overexpression of c-myc and related proteins; loss of differentiation markers such as TGF-b II receptor and retinoic acid receptor; and alteration of angiogenesis proteins such as VEGF overexpression. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors.

Adult↗

PubMedDate not supplied

Increased expression of angiogenic markers in patients with seasonal allergic rhinitis.

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. METHODS: Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. CONCLUSION: There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.

Adult↗

PubMed1990

[Experimental study of an axial vascularized pedicle flap induced in rats].

The authors report an experimental study about induced flaps in rats. The aim of this study is to determine that neoangiogenesis can be formed from surgically introduced pedicle. Two main groups were studied: in the first one the arteriovenous pedicle was be anastomased at its distal end, in the other, an arteriovenous loop was created microsurgically. In both groups we obtained good results and the flaps stayed alive. Neoangiogenesis from the surgically introduced axial pedicle was observed. The prospects in human pathology are interesting to consider, for the surgeon might be liberated from the narrow anatomic limits imposed by vascular territories, by creating a suitable flap anywhere in the body.

Graft Survival↗

PubMedDate not supplied

Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic osteosarcoma.

BACKGROUND: A need exists to stratify patients with nonmetastatic osteosarcoma into risk subcategories to administer risk-adapted therapy. Intratumoral angiogenesis determined at diagnosis may have a prognostic significance in this malignancy. PATIENTS AND METHODS: The authors performed a retrospective immunohistochemical study on archival pathologic material from patients with nonmetastatic osteosarcoma, excluding patients with purely chondroblastic tumors associated with hypovascularity of the cartilaginous stroma. Representative sections from the diagnostic biopsies were stained with a murine monoclonal antibody directed against CD34, an endothelial cell marker. Two pathologists unaware of the patients' long-term outcome counted microvessels in 10 microscopic fields from the most active areas of neovascularization. RESULTS: Between March 1988 and December 1996, 15 girls and 14 boys (median age 12.6 y, range 4.3-18.3) were identified. Seven patients had died of metastatic disease at a median of 3.4 years (range 0.8-7.4) after diagnosis; 22 were alive with no evidence of disease at a median follow-up of 6.8 years (range 2.7-11.4). There was no significant difference in the number of microvessels per field (pathologist 1, median 19 vs. 18.5; pathologist 2, median 15 vs. 10) between survivors or patients who died of metastatic disease. The correlation between the measurements of the two pathologists was excellent (correlation coefficient 0.87). CONCLUSIONS: Intratumoral neovascularization determined at diagnosis does not correlate with long-term outcome in patients with nonmetastatic osteosarcoma. A prospective study is necessary to confirm these results.

Adolescent↗

PubMed2005

[Effect of neutralizing anti-VEGF antibody on genesis of murine type II collagen-induced arthritis].

AIM: To understand the effect of neutralizing anti-vascular endothelial growth factor (VEGF) antibody on the genesis of murine type II collagen (CO II)-induced arthritis (CIA). METHODS: mice DBA/1J (8-10 weeks) were given intradermal injection chick tape II collagen to set up the murine CIA model. The incidence of CIA and arthritis index were measured and the pathologic changes of articular tissue were observed after the injection of neutralizing anti-VEGF antibody. RESULTS: The anti-VEGF antibody could notably inhibit the genesis and severity of arthritis (P<0.05) at the early stage of CIA formation; while it made no difference after CIA was completely formed. CONCLUSION: Anti-VEGF neutralizing antibody can significantly inhibit synovial fibroblast proliferation, neovascularization and angeitis genesis, which made it a promising agent for RA treatment.

Animals↗

PubMed1996

Neoangiogenesis: a putative marker of malignancy in non-small-cell lung cancer (NSCLC) development.

Several studies have documented a relevant prognostic role of microvessel count (MC) in non-small-cell lung carcinomas (NSCLC). However, no evidence has been reported about the involvement of neo-angiogenesis in the development of bronchial cancers. The aim of this study was to analyze microvessel density both in normal and in pathological features of the bronchial tree detected concomitantly with carcinomas. In a group of 34 patients resected for NSCLC, 48 bronchial lesions (hyperplasia, squamous metaplasia, moderate dysplasia and in situ carcinoma) were identified. In addition, 20 samples of normal bronchial epithelium from the same patients were analyzed. A monoclonal antibody was used in order to identify microvessels in the most intense areas of neovascularization from the bronchial specimens. MC was also analyzed in invasive components. An increased number of microvessels was observed from normal to dysplastic epithelium, including in situ carcinoma. Mean MC was significantly lower in normal, hyperplastic and squamous metaplastic epithelium than in dysplastic epithelium and in situ carcinoma. In particular, no differences were observed between normal and hyperplastic/metaplastic components, whereas a statistically significant difference appeared between the latter and dysplastic lesions. Moderate dysplasia and in situ carcinoma showed a number of microvessels in the lamina propria of their mucosa which were not significantly different from the invasive component, whereas hyperplastic/metaplastic lesions presented a much lower number of microvessels than invasive cancer. From these data it appears that normal bronchial epithelium and lesions associated with cancers of the bronchial tree show neovascularization in their stromal component. Hyperplasia and squamous metaplasia, unlike dysplasia and in situ carcinoma, show a low microvessel count, and they cannot represent precursor or incipient changes in the bronchial epithelium before the fully developed in situ stage has also been reached.

Carcinoma in Situ↗

PubMed2003

Angiogenesis in anal warts, anal intraepithelial neoplasia and anal squamous cell carcinoma.

INTRODUCTION: Most cases of anal carcinoma seem to develop from high grade anal intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre-invasive epithelial genital lesions (e.g. those of the cervix and vulva) have been shown to be associated with increased angiogenesis. In this study we examined biopsies of anal lesions ranging from warts to invasive anal carcinoma, with the aim of assessing the degree of angiogenesis in pre-invasive anal lesions. METHOD: Samples from 70 patients (51 male) who had undergone excision biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from normal HIV-anal skin were used as controls. The samples were stained for von Willebrand factor, a specific marker of endothelial cells. Angiogenesis was measured by microvessel density (MVD) analysis, quantifying the microvessels in the stroma adjacent to the epithelial lesion. RESULTS: There was a statistically significant (P < 0.001) progressive increase in MVD between low grade AIN, high grade AIN and anal SCC. The difference in MVD between normal skin, warts and low grade AIN was not statistically significant. CONCLUSION: There are progressive abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those found in cervical and vulvar pathology. These findings may have biological, prognostic and therapeutic implications.

Anal Canal↗

PubMed1998

AIDS-associated Kaposi's sarcoma.

In less than two decades, the disease mechanisms have been elucidated and hypotheses for innovative treatment have been developed. Our understanding of the sarcoma's pathogenesis has led directly to general knowledge of the physiology and pathology of angiogenesis. Hence, it can be expected that new treatments for all cancer patients may someday emerge from clinical intervention trials for the AIDS-related disease.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Cyclooxygenase-2: a therapeutic target in angiogenesis.

Angiogenesis has a role in the pathogenesis of several disorders, including cancer, chronic inflammatory diseases and retinopathies. Recent evidence demonstrates that the production of prostanoids by cyclooxygenase-2 (COX-2) promotes the expression of pro-angiogenic factors. Furthermore, inhibition of COX-2 by non-steroidal anti-inflammatory drugs leads to restricted angiogenesis and downregulated production of pro-angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor. These findings suggest that COX enzymes could be important therapeutic targets in the treatment of pathological angiogenesis.

Angiogenesis Inhibitors↗

PubMed1991

Microsurgical management of neovascularisation secondary to posterior segment ischaemia.

Structural, metabolic and functional rehabilitation of eyes affected by the haemorrhagic and tractional sequelae of neovascularisation secondary to posterior segment ischaemia is discussed. Microsurgical management must pay due attention not only to the mechanical but also to the underlying cell-biological implications of the surgical pathology. The appropriateness of case selection for surgery rests upon the likelihood of successful technical and functional outcomes and also upon the overall visual status of the patient, issues of particular relevance to diabetes.

Diabetic Retinopathy↗

PubMed1990

Developing testicular microvasculature in the golden hamster, Mesocricetus auratus: a model for angiogenesis under physiological conditions.

The ultrastructure of the developing testicular microvasculature in the testes of immature (3, 5, 8, 10, 12, 16, 20, 25, 30 and 35 days old) golden hamsters was examined and compared to the testicular microvasculature of adult (3 months old) hamsters. In addition, in 16- to 35-day-old hamsters vascular permeability was studied after localization of injected horseradish peroxidase (HRP). Angiogenic processes were present in the testes of all examined immature hamsters and were most conspicuous between 8 and 25 days of age. These processes were absent in the testes of 3-month-old hamsters. On days 3 and 5, few undifferentiated blood vessels with activated endothelium were present in the interstitial spaces. Endothelial cell migration started from these 'mother vessels' and led to invasion of intertubular spaces by vascular sprouts, before vascularization of peritubular spaces occurred (after day 12). Sprouting endothelial cells were identified by the presence of a basal lamina and characterized by abundant cytoplasm and cell organelles. HRP-positive slits were seen in developing vessels, which opened to form the vascular lumen. HRP exited the vascular lumen through unspecialized endothelial contacts and micropinocytotic vesicles. By day 16, the blood-testis barrier prevented HRP from entering the seminiferous tubules beyond the basal compartment. By days 30 and 35 most testicular microvessels and at the age of 3 months all testicular microvessels were of the mature type, with narrow inactive endothelium and specialized cell contacts (including tight junctions). These results demonstrate that the postnatal vascularization of the testis in the golden hamster is a timed complex process. Due to high permeability, vascular sprouts are likely to influence the metabolic situation and thus the maturation processes of the testis. Angiogenesis in the golden hamster testis shares typical morphological features with angiogenic processes in other organs and species under various pathological and physiological conditions. We therefore conclude that the postnatal testis can be viewed as a physiological model of angiogenesis.

Animals↗

PubMed2002

[Observation of the microstructure and ultrastructure of microvessels induced by OS-732 cell line].

OBJECTIVE: To observe the characteristics of the microstructure and ultrastructure of the microvessels induced by human osteosarcoma cell line (OS-732). METHODS: OS-732 cells were inoculated into the chick embryo chorioallantoic membrane to induce the growth of microvessels, the microstructure and ultrastructure of which were observed using dissecting microscope, light microscope and transmission electron microscope. RESULTS: OS-732 cell line was strongly angiogenic, and newly generated capillaries converging upon the tumor were visualized under dissecting microscope. Observation with transmission electron microscope found that the wall of the microvessels deficient in elements of smooth muscles was consisted of a monolayer of vascular endothelial cells with widened gaps in between, and the basement membrane appeared irregular. CONCLUSION: The microvessels induced by tumors have pathological and physiopathological characteristics consistent with the tumors, and setting the microvessels as a therapeutic target against osteosarcoma may help improve the prognosis of patients with this disease.

Animals↗

PubMed2004

KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth.

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play a central role in angiogenesis, which is necessary for solid tumors to expand and metastasize. Specific inhibitors of VEGFR-2 tyrosine kinase are therefore thought to be useful for treating cancer. We showed that the quinazoline urea derivative KRN633 inhibited tyrosine phosphorylation of VEGFR-2 (IC50 = 1.16 nmol/L) in human umbilical vein endothelial cells. Selectivity profiling with recombinant tyrosine kinases showed that KRN633 was highly selective for VEGFR-1, -2, and -3. KRN633 also blocked the activation of mitogen-activated protein kinases by VEGF, along with human umbilical vein endothelial cell proliferation and tube formation. The propagation of various cancer cell lines in vitro was not inhibited by KRN633. However, p.o. administration of KRN633 inhibited tumor growth in several in vivo tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. KRN633 also caused the regression of some well-established tumors and those that had regrown after the cessation of treatment. In these models, the trough serum concentration of KRN633 had a more significant effect than the maximum serum concentration on antitumor activity. KRN633 was well tolerated and had no significant effects on body weight or the general health of the animals. Histologic analysis of tumor xenografts treated with KRN633 revealed a reduction in the number of endothelial cells in non-necrotic areas and a decrease in vascular permeability. These data suggest that KRN633 might be useful in the treatment of solid tumors and other diseases that depend on pathologic angiogenesis.

Angiogenesis Inhibitors↗

PubMed1990

Increased angiogenesis in diabetes.

Rats with streptozotocin-induced diabetes mellitus showed a 3.4-4.5 times increased angiogenic response following mast-cell activation in situ as compared with age-matched normal controls. The test tissue used was the mesenteric window, which we have previously exploited as a quantitative angiogenesis assay. In the present study two independent techniques for quantifying the angiogenic response showed essentially the same result. The finding of a pathologically increased angiogenic reaction in the diabetic animals is noteworthy since some of the most harmful complications of diabetes in man relate to proliferative vascular lesions.

Animals↗

PubMed1993

Scatter factor induces blood vessel formation in vivo.

Scatter factor (also known as hepatocyte growth factor) is a glycoprotein secreted by stromal cells that stimulates cell motility and proliferation. In vitro, scatter factor stimulates vascular endothelial cell migration, proliferation, and organization into capillary-like tubes. Using two different in vivo assays, we showed that physiologic quantities of purified native mouse scatter factor and recombinant human hepatocyte growth factor induce angiogenesis (the formation of new blood vessels). The angiogenic activity was blocked by specific anti-scatter factor antibodies. Scatter factor induced cultured microvascular endothelial cells to accumulate and secrete significantly increased quantities of urokinase, an enzyme associated with development of an invasive endothelial phenotype during angiogenesis. We further showed that immunoreactive scatter factor is present surrounding sites of blood vessel formation in psoriatic skin. These findings suggest that scatter factor may act as a paracrine mediator in pathologic angiogenesis associated with human inflammatory disease.

Animals↗

PubMed2004

Immunodetection and quantification of vascular endothelial growth factor receptor-3 in human malignant tumor tissues.

Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme-linked immunosorbent assay (ELISA) for the quantification of VEGFR-3 in different human cell and tissue lysates. A combination of the goat polyclonal anti-VEGFR-3 antibody and the mouse monoclonal anti-human VEGFR-3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2-25 ng/ml. The assay was specific for VEGFR-3, with no cross-reactivity to VEGFR-1 or VEGFR-2. Complex formation with VEGF-C and VEGF-D had no effect on the sensitivity of the assay. The VEGFR-3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14-fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR-3 were in the range of 0.6-16.7 ng/mg protein. Importantly, the level of VEGFR-3 protein detected in the ELISA correlated significantly with the number of VEGFR-3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR-3-positive vessel density. The protein levels of VEGFR-3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF-C (p<0.001), or biological active, free VEGF-A (p<0.0001), but not with VEGFR-1 or total VEGF-A. This assay provides a useful tool for the investigations of the expression levels of VEGFR-3 in physiological and pathological processes, particular in cancer and in lymphangiogenesis-related disease.

Animals↗

PubMed2002

Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway.

Pleiotrophin (PTN the protein, Ptn the gene) is a 136 amino acid secreted heparin-binding cytokine that signals diverse functions, including lineage-specific differentiation of glial progenitor cells, neurite outgrowth, and angiogenesis. Pleiotrophin gene expression is found in cells in early differentiation during different development periods and upregulated in cells with an early differentiation phenotype in wound repair. The Ptn gene is a protooncogene. It is strongly expressed in different human tumor cells and expression of the Ptn gene in tumor cells in vivo accelerates growth and stimulates tumor angiogenesis. Separate independent domains have been identified in PTN to signal transformation and tumor angiogenesis. Pleiotrophin is the first ligand of any of the known transmembrane tyrosine phosphatases. Pleiotrophin inactivates the receptor protein tyrosine phosphatase (RPTP) beta/zeta. The interaction of PTN and RPTP beta/zeta increases steady-state tyrosine phosphorylation of beta-catenin. Pleiotrophin thus regulates both normal cell functions and different pathological conditions at many levels. It signals these functions through a transmembrane tyrosine phosphatase.

Amino Acid Sequence↗