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PubMedDate not supplied

Prognostic relevance of microvessel density in colorectal tumours.

The importance of angiogenesis as a prognostic marker has been examined in 111 colorectal cancer patients with a minimum follow-up of 5 years. Tumour sections were immunostained with pan-endothelial antibody to CD31. Microvessels were identified and counted in 5 separate areas of highest vascularity ( ). Analysis of the data showed that the survival was not significantly affected by tumour site, size, grade, patients' age or gender. However, a statistically significant correlation was found between microvessel density (MVD) and survival: patients with an increased number of microvessels survived longer than those with a low number of microvessels (p=0.0007). Therefore, paradoxically, unlike other tumour types, in colorectal cancer MVD appears to be an indicator of good prognosis. The reasons that MVD correlates with good or poor prognosis are likely to vary in different tumours. For instance a frequent difficult issue in colon cancer is the presence of ulceration and adjacent severe inflammation which by itself can increase vascularity. Furthermore, overall prognosis will also depend on other factors, such as oncogenes, extracellular matrix components, adhesion molecules, growth factors, degree of apoptosis and the mode of metastatic spread.

Adult↗

PubMedDate not supplied

Correlation between microvessel density and tumor cell proliferation with clinical factors in breast carcinomas.

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.

Adult↗

PubMed1999

Pericytes of term human foeto-placental microvessels: ultrastructure and visualization.

Placental microvessels examined by transmission electron microscopy showed many pericytes and pericyte foot processes included in the basement membrane. The foot processes were distinct from the endothelial cell extensions because of their lighter staining, their content of reticulum endoplasmic, their scarcity of microfilaments and their separation from endothelial cells by basement membrane material. Some of these features were held in common with early villous perivascular cells and pericytes from other microvascular beds. Denudation of the villi by dissection allowed the microvascular basement membrane to be reached and pericytes to be identified by scanning electron microscopy as large cells with extensions apposed to microvessels. Similarly, a two-step collagenase-dispase digestion with an intermediate Percoll gradient separation progressively removed the trophoblast and the stroma down to the microvessels. Pericyte-like cells were observed lying over the microvessels that exhibited some terminal dilatations where endothelial cells were still surrounded by the basement membrane. The origin and the potential functions of the pericytes (contractility, basement membrane secretion, angiogenesis and phagocytosis) in the placental vascular bed are discussed.

Collagenases↗

PubMed1999

Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients.

Nitric oxide (NO) is involved in tumor cell apoptosis and has additional effects on tumor blood flow, immune responses, and angiogenesis. We, therefore, studied endothelial cell NO synthase (ecNOS) protein expression in a retrospective series of 118 patients with primary invasive breast cancer. Immunocytochemically stained paraffin sections were used for determining the frequency of (a) tumor cells, (b) intratumoral microvessels, and (c) peritumoral microvessels that were positive for ecNOS. A high density of ecNOS positive microvessels in the normal tissue surrounding the tumor (measured by the variable PEMVD) was associated with significantly better recurrence-free and overall survival. The prognostic significance was observed in a representative series of premenopausal patients and was independent of other factors, including lymph node status. The counting procedure was highly reproducible and correlated to stereological measurements but was influenced by heterogeneity of the tissue samples. Analyzing two sections per patient improved the discriminative power by reducing the influence of tissue heterogeneity and produced highly significant results (recurrence-free survival, P < 0.001; overall survival, P < 0.0001). Immunoreactive ecNOS in microvessels is an independent prognostic factor in breast cancer and may reflect a mechanism of endothelial defense against invasion by tumor cells. Individual variations in ecNOS may be related to environmental, hormonal, and genetic factors and could represent a therapeutic target.

Adult↗

PubMed2000

Expression of vascular endothelial growth factor and microvessel density in head and neck tumorigenesis.

Angiogenesis is a fundamental process in tumor growth and metastasis, and its significance and that of vascular endothelial growth factor (VEGF) expression as prognostic indicators have been documented for various types of human tumors. However, the mechanisms responsible for angiogenesis in head and neck squamous cell carcinoma are not well defined. To examine the relationship between angiogenesis and the phenotypic progressions of head and neck tumorigenesis, we used immunohistochemistry to analyze VEGF expression and microvessel density in 70 paraffin-embedded specimens that contained adjacent normal epithelium, premalignant lesions, or both from 57 patients with head and neck squamous cell carcinoma. Ten samples of normal oral mucosa were obtained from people who did not smoke or drink alcohol and included in the analysis as normal controls. Microvessel density was evaluated by averaging 10 microscopic fields (x400) in a defined area of each specimen. The degree of VEGF expression was assessed on a cell-by-cell basis in 10 microscopic fields (x200) in a defined area on a scale ranging from 0 (no expression) to 3+ (highest level of expression). In addition, the weighted mean index of VEGF expression was calculated. The mean +/- SD weighted mean index of VEGF expression in normal control epithelium (1.10 +/- 0.38, n = 10) was higher than it was in adjacent normal epithelium (0.82 +/- 0.27, n = 13; P = 0.04). VEGF expression decreased as samples ranged from normal adjacent epithelium to hyperplasia (0.78 +/- 0.28, n = 21), mild dysplasia (0.70 +/- 0.29, n = 28), moderate dysplasia (0.67 +/- 0.29, n = 11), severe dysplasia (0.51 +/- 0.39, n = 6), and squamous cell carcinoma (0.20 +/- 0.27, n = 70; overall P = 0.0001). VEGF expression was two times lower in cases with nodal disease (0.17 +/- 0.26, n = 29) than it was in nonnodal disease (0.32 +/- 0.29, n = 16; P = 0.02). Microvessel density showed no significant difference from adjacent normal epithelium premalignant lesions to cancer. In tumor, no correlation was seen between VEGF expression or microvessel density and differentiation, primary tumor site, T stage, or smoking status. These findings indicate that VEGF expression is down-regulated during head and neck tumorigenesis. However, further studies are required to better understand the mechanism of VEGF down-regulation in head and neck tumorigenesis.

Adult↗

PubMed2002

Decreased suburethral prostatic microvessel density in finasteride treated prostates: a possible mechanism for reduced bleeding in benign prostatic hyperplasia.

PURPOSE: We evaluated the influence of finasteride on prostatic microvessel density to elucidate a mechanism of decreased bleeding in finasteride treated patients with hematuria secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 22 patients with clinical BPH and gross hematuria who underwent prostate reductive surgery between 1998 and 2000 were prospectively evaluated. The prostate from 10 finasteride treated and 12 untreated patients was immunohistochemically stained for CD-34. Microvessel density analysis was performed by quantifying positive stained blood vessels located within the stroma of hyperplastic nodules as well as in the suburethral portion of the prostate. RESULTS: Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively). CONCLUSIONS: Finasteride significantly decreases suburethral prostatic microvessel density in patients with BPH, which may explain its efficacy for decreasing BPH associated bleeding.

Aged↗

PubMed2002

[The role of specific endothelial granules in changes of myocardium microvessel reperfusion at open-heart operations under hypothermia].

For patients with congenital heart defects, a comparative analysis was carried out of specific endothelial granules and morphological properties of perfusion capacity of microvessels at various stages of reperfusion after prolonged circulatory arrest. At all stages of reperfusion, the quantity of specific granules in microvessel endothelium dramatically dropped, as compared with the control group. At the early stages of reperfusion, the level of granule exocytosis does not lead to any statistically significant changes in perfusion characteristics in the right atrium microvessels, as compared with the control group. Conversely, at the late stages of reperfusion, degranulation of endothelial cells is enhanced, and physiological mechanisms intended to remove the microvessels from circulation are replaced with pathological ones. These results suggest the existence of a threshold in exocytosis of specific endothelial granules, whose exceeding may switch on some pathological mechanisms in blood flow regulation.

Cell Degranulation↗

PubMed2000

[Relationship between vascular endothelial growth factor expression and microvessel density in hepatocellular carcinomas and their surrounding liver tissue].

The relationship between vascular endothelial growth factor (VEGF) expression and microvessel density was studied with immunohistochemical method in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue. The positive rate of VEGF in HCCs was significantly lower than in surrounding liver tissues (66.7% vs. 85.4%, P < 0.05). There was no significant difference between HCC and pericarcinomatous liver tissue on expressive intensity of VEGF. The positive signal of VEGF was mainly localized in cytoplasma of cancer cells, pericarcinomatous hepatocytes, and vascular endothelial cells. The microvessel density in HCC was higher than in pericarcinomatous liver tissue and closely correlated to differentiated degree of cancer cells (rs = 0.5870; rs = 0.8235). The poorer cancer cell differentiation, the higher microvessel density. The results suggest that VEGF may not be the sole factor that stimulates angiogenesis in HCC genesis and development. To detect microvessel density in judging prognosis and biological behavior of HCC is more important than that of VEGF.

Adult↗

PubMed2000

[A morphometric study on the microvessel in oral submucous fibrosis].

To investigate the pathologic change of the microvessel in oral submucous fibrosis(OSF), the pathologic buccal tissues of 27 patients with OSF were studied by using immunochemical method. Microvessel quantity(MVQ), quantity density(QD), microvessel area(MVA) and area density(AD) were determined by means of computer-aided image analysis system. The results showed the increase in MVQ and QD in the early stage and the decrease in MVQ, QD, MVA and AD in the middle stage and the late stage. The authors concluded that presence of microvessel hyperplasia occurred in the early stage of OSF.

Capillaries↗

PubMed2002

[Microvessel density index as a prognostic factor in a low histological differentiation stage of endometrial carcinoma].

OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated with tumor growth and metastasis. Studies of angiogenesis in breast, prostate and lung cancer showed that neovascularisation correlates with likelihood of metastasis and recurrence. Our study was to evaluate microvessel density as a prognostic factor in endometrial cancer. METHODS: Between 1995-1999, 58 women were treated for endometrial carcinoma. The primary treatment consisted of total abdominal hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy. The microscopic examination of paraffin blocks showed the areas of the deepest myometrial invasion. The microvessels within the invasive cancer were highlighted by means of immuno-cytochemical staining to detect CD-31 antigen. RESULTS: Microvessel count was related to likelihood of recurrence. We found statistically significant differences between patients who died after operation and patients with nonrecurrence process. All patients were in the same stage and grade of endometrial carcinoma. CONCLUSION: Microvessel density index seems to be an important factor for planing postoperation treatment in endometrial carcinoma.

Adult↗

PubMed2001

[Correlation of tumor microvessel density with prognosis in laryngopharyngeal malignant melanoma].

OBJECTIVE: To investigate the relationship between microvessel density and clinicopathology, as well as the prognosis in pharyngo-laryngeal malignant melanoma. METHODS: Specific endothelial cell markers with immunohistochemistry and microvessel density with morphometry in 28 cases of laryngopharyngeal malignant melanoma. RESULTS: There was no correlation between the microvessel density (MVD) and the tumor size, Clark grade, as well as Breslow grade; however, significant correlation was found between the MVD and the AJC's grade, as well as the proliferating cell nuclear antigen (PCNA) labelling index. Microvessel counts were associated with overall survival by Kaplan-Meier analysis. An average vessel count of less than 36.5 (x 200) suggested a better survival, but a higher vessel count of more than 36.5 (x 200) showed a trend to worse the overall survival. CONCLUSION: The results suggest a significant relationship between MVD and prognosis; moreover, MVD may be a useful prognostic indicator in laryngopharyngeal malignant melanoma.

Adult↗

PubMed2003

High heparanase activity in multiple myeloma is associated with elevated microvessel density.

Heparanase is an enzyme that cleaves heparan sulfate chains of proteoglycans, and its expression has been associated with increased growth, metastasis, and angiogenesis of some tumors. Because myeloma tumor cells express high levels of the syndecan-1 heparan sulfate proteoglycan and because these tumors grow as highly vascularized aggregates within the bone marrow, we analyzed the activity, expression, and function of heparanase in myeloma patients. Analysis of heparanase activity in the plasma isolated from bone marrow biopsies of 100 patients reveals 86 positive for heparanase activity and 14 negative. The bone marrow samples can be further divided into three categories of heparanase activity, high activity (42 patients), low activity (44 patients), and negative (14 patients). In contrast to the bone marrow plasma, levels of heparanase activity in peripheral blood plasma of 29 myeloma patients were either negative or low, suggesting that in multiple myeloma, heparanase functions in the local microenvironment of the bone marrow and its activity is not significantly elevated systemically. Immunohistochemistry reveals that patients with high levels of heparanase activity often have tumor cells with intense staining for the enzyme. Interestingly, a marked heterogeneity among tumor cells was noted, with clusters of heavily stained cells surrounded by cells with weak or negative staining for heparanase. Analysis of microvessel density reveals a strikingly higher concentration of vessels in patients with high heparanase activity (78.96 vessels/mm(2)) as compared with patients negative for heparanase activity (25.03 vessels/mm(2)). When human myeloma cells transfected with the cDNA for heparanase are implanted in severe combined immunodeficient (SCID) mice, the resulting tumors exhibited a significantly higher microvessel density than did tumors established with control cells. Thus, expression of heparanase appears to play a direct role in enhancing microvessel density in these myeloma tumors. Because heparanase is known to stimulate angiogenesis, and because high microvessel density is associated with poor prognosis in myeloma, we conclude that heparanase expression likely plays an important role in regulating the growth and progression of myeloma, and that therapies designed to block heparanase activity may aid in controlling this cancer.

Animals↗

PubMed2005

Maspin and c-erbB-2 expression in correlation with microvessel density in invasive ductal breast cancer.

Maspin is a unique member of the serpin family involved in regulation of cell migration, apoptosis and angiogenesis in breast and prostate cancers. In this study maspin expression in comparison with c-erbB-2 (HER2/neu) oncogene expression and microvessel density was investigated. The examined material included specimens of primary invasive ductal breast cancer derived from 69 patients. They were analyzed immunocytochemically to assess maspin and c-erbB-2 expression, as well as microvessel density using endothelium marker CD31. In the studied cancers, maspin expression in cancer cells was detected in more than half of the cases (50.73%). Although statistically insignificant (p=0.27), maspin expression showed decreasing tendency with the increase of tumor grade. C-erbB-2 oncogene expression was observed in 78.26% of the examined cancers. Statistically significant positive correlation was found between c-erbB-2 expression and tumor grade (p<0.005). Analysis of the dependence between maspin and c-erbB-2 expression exhibited statistically significant inverse correlation (p<0.001). Mean microvessel density (MVD) of the studied cancers was 71.64 (SD=19.36). MVD decreased with the increase of maspin expression, whereas in the cases showing c-erbB-2 overexpression MVD was clearly higher. Both correlations were statistically significant (p<0.005). In conclusion, it could be stated that increase in maspin expression is associated with weaker expression of c-erbB-2 oncogene and lower microvessel density, which implies a significant role of maspin in tumor biology. However, the exact mechanism of maspin action (including its potential role in angiogenesis), as well as the assessment of its prognostic significance in breast cancer require further studies.

Aged↗

PubMed1992

Diminished leukocyte-endothelium interaction in tumor microvessels.

Leukocyte-endothelium interaction in vivo consists of the rolling of leukocytes along the vascular wall and, under certain conditions, their adherence to endothelial cells. In a rat tumor microcirculation model (mammary adenocarcinoma implanted in rat skinfold window chamber), we demonstrated that this interaction, measured as flux of rolling leukocytes and density of adhering leukocytes, was significantly reduced in tumor microvessels compared to normal microvessels, both under control conditions and during inflammation induced by N-formylmethionylleucylphenylalanine (1 microM), bacterial lipopolysaccharide (1 microgram/ml), or tumor necrosis factor alpha (500 units/ml). We also measured the blood flow shear rate in the tumor and normal microvessels and found that the difference in shear rate between the two types of microvessels could not account for the differences in leukocyte-endothelium interaction. The diminished leukocyte-endothelium interaction in tumors under various stimulated conditions suggests that a number of adhesion molecules may not be expressed properly on tumor endothelial cells.

Adenocarcinoma↗

PubMed2006

Velocity profiles in the rat cerebral microvessels measured by optical coherence tomography.

In order to analyze cerebral hemodynamics and its change following neural activation, the cross-sectional profiles of blood flow velocity in the rat pial microvessels and their temporal changes were measured in vivo using Doppler OCT technique (Doppler optical coherence tomography). The OCT system used in this study has axial resolution of 11 microm and lateral resolution about 14 microm in the cortical tissue. The velocity distributions along the vertical diameter of pial microvessels in a cranial window of the rats were measured at short time intervals by scanning the OCT sampling point repeatedly. The velocity profiles obtained in the pial arterioles were parabolic at any phase, although the centerline velocity pulsated following heart beats with amplitude as large as 50% of the temporal mean velocity. It indicates that the blood flow in the pial microvessels is a quasi-steady laminar flow, which is consistent with the flow expected for the case of a small Reynolds number and a small frequency parameter. The stimulus-induced increase in velocity pulsation was much larger than the increase in the mean velocity, which places a restriction on the mechanism of regulating the regional cerebral blood flow and blood volume. The results obtained in this study showed that the Doppler OCT has a potential of measuring velocity profiles and their temporal changes with both high temporal and spatial resolutions for the pial microvessels with diameter up to 200 microm.

Animals↗

PubMed2005

Studies on drug metabolizing enzymes during arteether treatment of Plasmodium yoelii nigeriensis infected mice cerebral microvessels.

Human cerebral malaria is caused by a protozoan parasitic with no cure till date. The isolation of brain capillaries i.e. microvessels has permitted the in vitro study related to cerebral function. Microvessels were isolated from normal and P. yoelii infected mice brain cortex and subjected to biochemical characterization by the following enzyme markers viz alkaline phosphatase, gamma-glutamyI transpeptidase and monoamine oxidase and electron microscopically. Limited studies have been carried out in relation to drug metabolizing enzymes in cerebral microvessels of rodents. The present studies have been carried out in relation to status of drug metabolizing enzymes during P. yoelii infection in cerebral microvessels of mice. The data obtained depicted a clear cut impairment of cytochrome P450 (a terminal monooxygenase) and related indices viz b5, benzopyrene hydroxylase, aminopyrene-n-demethylase, aniline hydroxylase except NADH cytochrome e reductase which increased during P. yoelii infection in mice as compared to normal. Further the oral drug administration (arteether) treatment brought back the altered MFO system normal a week alter cessation of drug treatment.

Animals↗

PubMed2006

[Effects of sense vascular endothelial growth factor cDNA transfection on mononuclear chemotaxis protein-1 expression in rat pulmonary microvessel endothelial cells].

OBJECTIVE: To study the transformation characteristics of tight junction of microvessel endothelial cells in bleomycin (BLM) induced pulmonary fibrosis (PF), and the effects of vascular endothelial growth factor (VEGF) on mononuclear chemotaxis protein-1 (MCP-1) mRNA expression in pulmonary microvessel endothelial cells (EC). METHODS: Forty healthy rats were equally divided into a control and an experimental group in random. In the experimental group, PF were induced by BLM application. In each group, 10 rats were instilled by lanthanum sal at 3, 7, 14 and 28 d after BLM application, and lung samples were made and observed by transmission electron microscopy. The pulmonary microvessel EC of the other 10 rats in each group were preserved by tissue culture methods at the same time, and the cells were transfected with sense VEGF cDNA, and then MCP-1 mRNA expression was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) technique. RESULTS: Blood vessel endothelial cells of the control group were intact. The basement membrane was shown as a continuous line. Granules of lanthanum sal did not cross the tight junction of endothelial cells. The width of the junction gap in rats of the experimental group treated at different times was increased and lanthanum particles of high density were seen in the gap junction, particularly on day 3, and were distributed in the area of subendothelium. The MCP-1 mRNA expression in VEGF transfected microvessel EC was significantly higher than that of the control group (1.21 +/- 0.22 vs 0.36 +/- 0.06, P < 0.05). CONCLUSION: In BLM induced PF, the opening of the tight junction of EC, and the high expression of MCP-1 induce inflammatory cell infiltration and cytokine over-secretion, which in turn enhances proliferation of fibroblasts, one of the important factors underlying lung fibrosis.

Animals↗

PubMed1990

Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro.

We report here that rings of rat aorta embedded in gels of fibrin or collagen and cultured in MCDB 131, an optimized growth medium for microvascular endothelial cells, generate branching microvessels in the absence of serum or other soluble protein supplements. The angiogenic response is self-limited and can be quantitated by counting the newly formed microvessels daily in the living cultures. The microvascular growth curves are characteristic for each gel. Growth of microvessels in collagen gel peaks at the end of the 1st week and is followed by a rapid regression in the 2nd week. Fibrin gels, as compared with collagen, stimulate angiogenesis by 170%, support growth during the 2nd week, and protect the newly formed microvessels from early regression. Angiogenesis is inhibited by adding hydrocortisone to the culture medium. Conversely, a 230% stimulation of angiogenesis is obtained when aortic rings are cultured in collagen gels floating in serum-free medium conditioned by sarcoma 180 cells. Our results demonstrate that: (a) angiogenesis can be obtained reproducibly in serum-free culture; (b) serum-free culture is a sensitive method for testing the inhibitory or stimulatory effects of soluble or matrix factors on angiogenesis; (c) the aortic ring model can be used as a quantitative assay for the study of angiogenesis under chemically defined culture conditions.

Animals↗