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Results for “Neovascularization, Pathologic”

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PubMed1997

Relationship of transforming growth factor beta 1 to angiogenesis in gastric carcinoma.

Transforming growth factor-beta (TGF-beta) comprises a group of multifunctional regulatory proteins, whose effects include angiogenesis. The expression of TGF-beta 1 in gastric carcinomas (70 cases) has been determined and related to pathological features and microvessel count by immunohistochemical staining for TGF-beta 1 and Factor VIII related antigen. Prominent reactivity for TGF-beta 1 was associated with the depth of invasion (r = 0.2; p < 0.05) and increased microvessel count (r = 0.5; p < 0.05). Also, the microvessel count had a significant correlation with invasiveness (r = 0.34; p < 0.05) and lymph node metastasis (r = 0.28; p < 0.05). These findings indicate that TGF-beta 1 may have a role in tumor invasion and angiogenesis.

Adult↗

PubMed2003

Correlation of CT enhancement, tumor angiogenesis and pathologic grading of pancreatic carcinoma.

AIM: To study the correlation between pancreatic phase CT enhancement, intratumor microvessel density (MVD) and pathologic grading of pancreatic carcinoma and to evaluate the relationship between the degrees of CT enhancement and malignancy of pancreatic carcinoma. METHODS: Thirty four patients with pancreatic carcinoma underwent CT scanning before resection. The enhancement degrees and forms of tumor were observed in pancreatic phase. The operative sample was stained with HE and CD34 marked by immunohistochemistry. MVD and histopathological grades of pancreatic carcinoma were examined. CT enhancement of the tumor, MVD counting in hot spot areas of neoplastic parenchymal cells and pathological grades of pancreatic carcinoma were comparatively analyzed. RESULTS: Highly differentiated pancreatic adenocarcinoma was identified in 16 patients, moderately-differentiated tumor in 7 and poorly-differentiated in 11. Isodensity CT enhancement was demonstrated in 13 cases, slightly low density enhancement in 9, slightly low density enhancement with small cystic lesions in 9 and slightly low density enhancement with large cystic lesions in 3. The counting of MVD with CD34 marked by immunohistochemistry in hot spot areas of neoplastic parenchyma cells was small in 10 cases, medium in 16 and large in 8. The pathological grades correlated well with CT enhancement of the tumor (r=0.7857, P<0.001) and with MVD counting of tumor (r=0.3613, P<0.05). The CT enhancement of tumor correlated with MVD(r=0.6768, P<0.001). CONCLUSION: There is an obvious and significant correlation between CT enhancement, pathological grades and MVD number in the hot spot areas of tumor. The extent of CT enhancement is inversely proportional to the malignant degree of pancreatic carcinoma, and to the MVD number in the hot spot areas of neoplastic parenchyma. The MVD in the hot spot areas of neoplastic parenchyma cells can also reflect the prognosis of the patients, and is directly proportional to the malignant degree of pancreatic carcinoma.

Adult↗

PubMed2000

Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus.

Vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were examined by immunohistochemical staining in 117 cases of thoracic esophageal squamous cell carcinoma. Thirty-six (31%) of the 117 cases were evaluated as VEGF-positive. The average number of metastatic lymph nodes at surgery was 5.6 in the VEGF-positive cases and 3.0 in the VEGF-negative cases and was significantly higher in those with VEGF-positive cases (P = 0.04). The incidence of pathological tumor (PT)2-4 cases among the high-MVD cases was significantly higher than among the low-MVD cases (P = 0.01). MVD was 59.4 +/- 4.7 (mean +/- SE)/mm2 in the VEGF-positive cases and 47.9 +/- 3.8/mm2 in the VEGF-negative cases. The MVD of the VEGF-positive tumors was higher than that of VEGF-negative tumors, but the difference was not significant (P = 0.08). The survival rate of the patients with high-MVD tumors was significantly poorer than those with low-MVD tumors, and the survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.009 and P = 0.04, respectively). The cumulative survival rates in the VEGF-positive groups were found to be significantly poorer in the pT3 and pathological node (pN)1 groups when stratified according to pT factor (pathological T category) and pN factor (pathological N category) in the tumor-node-metastasis (TNM) classification. VEGF expression had the second highest hazard ratio in the multivariate analysis, after pN factor. These results indicate that VEGF is a useful marker for predicting the outcome in patients with more advanced esophageal squamous cell carcinoma. It seems that TNM factors and VEGF expression are important factors in the selection of appropriate treatments.

Adult↗

PubMedDate not supplied

Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma.

Tumor-associated macrophages (TAMs) have been shown to display both positive and negative effects on tumor growth of various cancer. In this study, TAMs were immunohistochemically labeled using CD68 antibody in 82 oral cancer. Macrophage index (MI) were analyzed in association with clinical and pathological factors, intratumoral microvessel density (IMVD) and angiogenic factors including VEGF and TP. Significantly higher number of CD68-positive cells was noted in oral cancer. TAM expressions were significantly associated with stages of invasion, IMVD, and angiogenic factors. These findings suggest that TAMs possibly play a role in angiogenesis during oral cancer progression.

Antigens, CD↗

PubMed2004

Targeting angiogenesis for mammary cancer prevention: factors to consider in experimental design and analysis.

An experimental model developed to investigate premalignant stages of breast cancer was used to establish a rationale for designing experiments that target angiogenesis for cancer prevention. Blood vessels were identified via CD31 immunostaining, and all vessels that occurred in a 50 microm wide region circumscribing each pathology were counted using a digital imaging technique. The blood vessel density associated with terminal end buds was unaffected by carcinogen treatment, whereas vessel density was higher in intraductal proliferations and ductal carcinoma in situ than in terminal end buds (P < 0.001) and total vascularity increased with morphologic progression. In comparison with intraductal proliferation or ductal carcinoma in situ, mammary carcinomas had higher vascular density in the tissue surrounding the cancer with a marked increase in the number of blood vessels <25 microm(2). These data suggest that antiangiogenic chemopreventive agents would inhibit cancer occurrence if initiated at any premalignant stage of the carcinogenic process. Because increased vascular density observed during premalignancy could be explained by the size expansion of the lesion and its encroachment on a preexisting blood supply, by pathology-associated vessel expansion, and/or by angiogenesis, it remains to be determined if antiangiogenic agents will reduce the prevalence of premalignant lesions or cause their accumulation by blocking conversion to carcinomas. Failure to recognize the patterns of vascularization that accompany morphologic progression could limit the success of efforts to target angiogenesis for cancer prevention and lead to misinformation about how agents that affect blood vessel formation or growth inhibit the carcinogenic process.

Angiogenesis Inducing Agents↗

PubMed2005

[The expression of hepatocyte growth factor and its receptor in brain astrocytomas].

OBJECTIVE: To investigate the expression of hepatocyte growth factor (HGF) mRNA and its receptor (c-Met) mRNA in brain astrocytomas and their relationships with tumor proliferation, angiogenesis, clinical pathology and prognosis. METHODS: The expression of HGF mRNA, c-Met mRNA in the resected tumor tissues of 76 patients with brain astrocytomas, 43 males and 33 females, aged 20 - 71, were detected by in situ hybridization. Immunohistochemistry technique was used to test the expression of proliferating cell nuclear antigen (PCNA) protein and the microvessel density (MVD) was determined by immunohistochemistry with monoclonal antibody against CD34. RESULTS: The positive rates of expression of HGF, c-Met and PCNA in low pathologic grades of brain astrocytoma were 34.5%, 44.8% and 15% +/- 9% respectively, and in high pathologic grades of brain astrocytoma were 34.5%, 44.8% and 48% +/- 12% respectively (P < 0.05). MVD in low and high pathologic grades of brain astrocytoma were 17 +/- 7 and 31 +/- 13 respectively (P < 0.05). The expression of HGF, c-Met, PCNA and CD34 was not related to sex, age, position of tumor and diameter of tumor. The expression of c-Met was related to the expression of HGF, PCNA and the MVD in the tumor tissues of these patients. The pathological grade, position of tumor, HGF, c-Met, PCNA, MVD had a significant influence on the survival time. CONCLUSION: HGF/c-Met plays an important role in the formation and progression of the brain astrocytoma and can promote tumor proliferation and intratumoral microvascular formation, and is closely related to the prognosis of the patients.

Adult↗

PubMed2006

Angiosonography in suspicious breast lesions with non-diagnostic FNAC: comparison with power Doppler US.

PURPOSE: The purpose of this study was to evaluate the accuracy of angiosonography in comparison with colour Doppler ultrasound (US) in the discrimination of suspicious breast lesions with nondiagnostic fine-needle aspiration cytology (FNAC). MATERIALS AND METHODS: Pre-operative Power Doppler US and angiosonography were prospectively performed in 20 suspicious breast lesions with non-diagnostic FNAC. A second-generation US contrast agent was utilised with a high-frequency transducer and a contrast-specific algorithm (low acoustic pressure CnTI). The enhancement characteristics of all lesions were analysed using qualitative and quantitative parameters obtained from time-intensity curves with the different imaging modalities. The final diagnosis was confirmed at pathology in all cases. Microvessel density (MVD) was assessed in the surgical specimen using CD34. RESULTS: The correct assessment of biological behaviour was achieved in all cases by angiosonography (sensitivity of 100%; specificity of 91%) and colour Doppler US (45% sensitivity; 78% specificity). MVD correlated with the biological behaviour. CONCLUSIONS: Angiosonography is more accurate than colour Doppler US in the correct assessment of biological behaviour of suspicious breast lesions.

Adult↗

PubMed2004

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.

Adult↗

PubMed2001

Pathologic assessment of the surgical specimen.

Despite the wealth of information obtained by conventional histology, long-term studies are needed to provide novel information on the correlation of pathologic findings with prognosis. Findings need to be correlated not only with PSA progression but with the more clinically important parameters of distant metastases and survival. Although conventional histology still will have a role in the evaluation of prostate cancer at radical prostatectomy and its correlation with outcome, it undoubtedly will be augmented by newer techniques. These developments must be approached critically and rationally to determine whether they provide additional prognostic information beyond that currently available using more conventional parameters.

Biomarkers, Tumor↗

PubMed2005

Angiogenesis in oral squamous cell carcinoma.

Many retrospective studies have recently shown that microvessel density could represent a valid independent prognostic factor for overall survival and disease-free survival for primary tumours. The fact that oral tumours with a higher microvessel density showed a tendency to present distant metastasis and a bad prognosis, suggested that angiogenetic activity would play a pivotal role also in oral carcinomas, exerting a negative effect on the clinical course and representing an independent negative prognostic factor also for this type of tumour. Based on these results, microvessel density was evaluated, in the present study, in 64 cases of squamous cell carcinoma of the oral cavity, using immunohistochemical analysis with anti-CD34 monoclonal antibody. Possible correlations between microvessel density and clinico-pathological parameters were analysed, such as: age, sex, tumour localization and size, TNM stage and histological grading. Statistical analysis has shown that microvessel density differs in the 3 histological groups (G1, G2, G3) (p = 0.0331), and between node-positive and node-negative patients (p < 0.0001). No statistical correlation was observed between microvessel density and other clinical parameters such as age, sex, tumour site and size.

Adult↗

PubMed2005

Angiogenesis in gliomas: biology and molecular pathophysiology.

Glioblastoma multiforme (GBM) is characterized by exuberant angiogenesis, a key event in tumor growth and progression. The pathologic mechanisms driving this change and the biological behavior of gliomas remain unclear. One mechanism may involve cooption of native blood vessels by glioma cells inducing expression of angiopoietin-2 by endothelial cells. Subsequently, vascular apoptosis and involution leads to necrosis and hypoxia. This in turn induces angiogenesis that is associated with expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) in perinecrotic pseudopalisading glioma cells. Here we review the molecular and cellular mechanisms implicated in HIF-1-dependent and HIF-1-independent glioma-associated angiogenesis. In GBMs, both tumor hypoxia and genetic alterations commonly occur and act together to induce the expression of HIF-1. The angiogenic response of the tumor to HIF-1 is mediated by HIF-1-regulated target genes leading to the upregulation of several proangiogenic factors such as VEGF and other adaptive response molecules. Understanding the roles of these regulatory processes in tumor neovascularization, tumor growth and progression, and resistance to therapy will ultimately lead to the development of improved antiangiogenic therapies for GBMs.

Animals↗

PubMed2006

Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma.

The prognosis of head-and-neck squamous cell carcinoma (HNSCC) has not been improved in the past 20 years. Validation of HNSCC biomarkers for targeted therapy has been hindered by a lack of animal models mimicking human HNSCC at both the pathological and molecular levels. Here we report that overexpression of K-ras or H-ras and loss of transforming growth factor-beta type II receptor (TGFbetaRII) are common events in human HNSCC. Activation of either K-ras or H-ras in combination with TGFbetaRII deletion from mouse head-and-neck epithelia caused HNSCC with complete penetrance, some of which progressed to metastases. These tumors displayed pathology indistinguishable from human HNSCCs and exhibited multiple molecular alterations commonly found in human HNSCCs. Additionally, elevated endogenous TGFbeta1 in these lesions contributed to inflammation and angiogenesis. Our data suggest that targeting common oncogenic pathways in tumor epithelia together with blocking the effect of TGFbeta1 on tumor stroma may provide a novel therapeutic strategy for HNSCC.

Animals↗

PubMedDate not supplied

Biological parameters for the choice of antiangiogenic therapy and efficacy monitoring.

Angiogenesis is a tightly controlled process which depends on the balance between stimulating and inhibiting factors. When this balance is disrupted, angiogenesis acquires a pathological meaning. The list of molecules able to induce angiogenesis is heterogeneous with respect to their chemical characteristics and biological properties. Quantitative measurement of tumor angiogenesis is necessary for the choice of therapeutic strategies and as an endpoint for antiangiogenic therapy. We are developing a quantitative RT-PCR with measures the expression of specific factors in real time. With the use of this rapid technique, measurement of the expression of the angiogenic factors and inhibitors is also possible in specimens as small as biopsies.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Interactions between cancer cells and the microvasculature: a rate-regulator for metastasis.

Hematogenous metastasis is a major consideration in the staging, treatment and prognosis of patients with cancer. Key events affecting hematogeneous metastasis occur in the microvasculature. This is a brief, selective review of some interactions involving cancer cells and the microvasculature in pathologic sequence, specifically: (1) intravasation of cancer cells; (2) the arrest of circulating cancer cells in the microvasculature; (3) cancer cell trauma associated with arrest; (4) microvascular trauma; (5) the inflammatory; and (6) the hemostatic coagulative responses associated with arrest, and finally (7) angiogenesis, leading to tumor vascularization. The evidence shows that through a series of complex interactions with cancer cells, the microvasculature acts as a rate-regulator for the metastatic process, in addition to providing routes for cancer cell dissemination and arrest sites for cancer cell emboli.

Cell Adhesion↗

PubMed2005

Delivery of antiangiogenic agents for cancer gene therapy.

The understanding that tumor growth and metastasis are angiogenesis dependent processes has led to interest in targeting tumor vasculature in anticancer therapy. Furthermore, recent insights into the molecular interactions that orchestrate physiologic and pathologic angiogenesis have resulted in a variety of antiangiogenic strategies. A gene therapy-mediated approach for the delivery of antiangiogenic agents has several advantages, including the potential for sustained expression. However, the choice of angiogenesis inhibitor, method of gene delivery, and target/site for transgene expression are important variables to be considered when designing this approach. Here we review the major alternatives within each of these categories and provide illustrative examples of their use in preclinical models.

Angiogenesis Inhibitors↗

PubMed2002

Diabetic microangiopathy: pathology and current understanding of its pathogenesis.

Recent drastic increase in diabetic population poses serious problems in both health sciences and socioeconomic conditions. The most important issue in the clinical practice of diabetic patients is the treatment and care of chronic complications. It is not fully clear, however, as to the pathophysiology of diabetic microangiopathy and its pathogenesis. Recent studies on microvessel pathology in diabetic patients and molecular analyses on the diabetic animal models disclosed novel features of the dynamic changes of specific organ pathology affected by diabetes and factors involved in its pathogenesis. Under long-term hyperglycemia, early stimuli elicit adaptive reactions of tissues showing acute inflammatory processes of vessel walls and then late irreversible and regressive changes of microangiopathy. Consequently, remodeling of vascular cells and excessive matrix production are cardinal feature. The precise mechanisms of how these tissue changes occur remain speculative; increased polyol pathway, excessive non-enzymatic glycation, increased protein kinase C activity, as well as oxidative stress are all interrelated for the cause and development of the microangiopathy.

Blood Vessels↗

PubMed1989

Role of growth factors in the formation of blood vessels.

The turnover of endothelial cells in the normal human adult male is very low, on the order of years. However, in a number of mainly pathological conditions endothelial cells rapidly proliferate, thereby giving rise to new blood vessels (a process called angiogenesis). Angiogenesis-inducing factors have been purified from normal and tumor tissues. Some of these factors are growth or chemotactic factors for endothelial cells. Others have no effect in vitro and are thought to act via indirect mechanisms. Growth and chemotactic factors are also secreted by endothelial cells themselves and may be involved in the development of the vascular wall. In addition they might play a role in atherosclerosis.

Angiogenesis Inducing Agents↗

PubMed1996

Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF) is a multifunctional cytokine which potently stimulates angiogenesis in vivo. VEGF/VPF expression is elevated in pathological conditions including cancer, proliferative retinopathy, psoriasis and rheumatoid arthritis. The angiogenesis associated with human tumors is likely a central component in promoting tumor growth and metastatic potential. The regulation of VEGF/VPF expression during tumor progression may involve diverse mechanisms including activated oncogenes, mutant or deleted tumor suppressor genes, cytokine activation, hormonal modulators, and a particularly effective activator, hypoxia. Understanding the diverse mechanisms by which tumor cells overexpress VEGF/VPF, and which mechanisms are operating in specific tumor types is important for the design of effective anti-cancer therapies.

Animals↗