Mean Microvessel Count Research Articles

Regeneration of emphysematous lungs using gelatin sheets that release basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) induces regeneration and neovascularization of the lungs. We conducted this study to demonstrate the regeneration of emphysematous lungs achieved by gelatin sheets that slowly release bFGF into the visceral pleura in a canine model. Porcine pancreatic elastase was used to induce bilateral lower lobe pulmonary emphysema in dogs. Slow-release bFGF gelatin sheets were attached to the visceral pleura of the left lower lobe via thoracotomy. The subjects were divided into two groups: one treated with gelatin sheets containing slow-release bFGF (bFGF+ group, n = 5), and the other, treated with only gelatin sheets (bFGF- group, n = 5). The subjects were euthanized after 28days and histologic lung assessment was performed. The results were evaluated in terms of the mean linear intercept (MLI) and microvessel count. The MLI was significantly shorter in the bFGF+ group than in the bFGF- group; (110.0 ± 24.38 vs. 208.9 ± 33.08μm; P = 0.0006). The microvessel count was not significantly different between the bFGF+ and bFGF- groups (12.20 ± 3.007 vs. 5.35 ± 2.3425; P = 0.075); however, it was significantly higher in the bFGF-attached lungs than in the emphysema group (12.20 ± 3.007 vs. 4.57 ± 0.8896; P = 0.012). Attaching gelatin sheets with slow-release bFGF to the visceral pleura induced lung regeneration and vascularization in a canine pulmonary emphysema model.

Does angiogenesis have a prognostic value in squamous cell carcinoma of the larynx?

Abstract Angiogenesis marks a tumour’s transition to a systemic disease. It is a useful prognostic and predictive factor; yet, its relationship to prognosis in squamous cell carcinoma of the larynx is controversial. Aim of this study was to evaluate the significance of angiogenesis in laryngeal squamous cell carcinoma. A prospective study was conducted in the Otorhinolaryngology Department of Ain Shams University. Patients with laryngeal cancer, between 2006 and 2012, were enrolled. After surgery, histopathological examination with grading of tumours and immunostaining with CD34 antibody was carried out. Patients were followed up for 2 years and reassessment with immunostaining was carried out for recurrent tumours. Eighty cases were included. Results showed that tumours associated with a higher mean microvessel count had a highly significant association with nodal metastasis, recurrence and subsites, with poorer prognosis. Results suggest that angiogenesis can be used as a prognostic factor in patients with laryngeal squamous cell carcinoma.

Relationship between microvessel count and clinicopathological characteristics and postoperative survival in patients with pancreatic carcinoma.

The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy. CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients. Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15). Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.

Immunohistochemical Comparative Analysis of Cell Proliferation and Angiogenic Index in Squamous Cell Carcinomas of the Tongue Between Young and Older Patients

Oral squamous cell carcinoma (SCC) is a malignant epithelial tumor that is uncommon in individuals younger than 45 years. This study compared the cell proliferation and angiogenic index in SCCs of the tongue between young and older patients. Forty SCCs of the tongue, 20 diagnosed in young patients (≤ 40 y) and 20 diagnosed in older patients (>50 y) were evaluated by immunohistochemistry. Cell proliferation was evaluated using the Ki-67 labeling index (LI). The angiogenic index was determined by microvessel count (MVC) using anti- von Willebrand factor antibody. The mean Ki-67 LI in SCCs of the tongue was 43.8% (range, 26.0% to 72.4%) in young patients and 42.5% (range, 9.0% to 59.4%) in older patients (P=0.968). No significant difference in the Ki-67 LI was observed in relation to clinical stage or histologic grade of malignancy in either group (P>0.05). The mean MVC in SCCs of the tongue was 24.3 (range, 8.6 to 51.6) in young patients and 25.6 (range, 5.4 to 42.4) in older patients (P=0.543). There was no significant difference in MVC in relation to clinical stage or histologic grade of malignancy in either group (P>0.05). In addition, no significant correlation was observed between the Ki-67 LI and the angiogenic index (P>0.05). The results of this study suggest that the more aggressive biological behavior of SCC of the tongue in young patients may not be related to a higher cell proliferation rate or a higher angiogenic index.

Immunohistochemical expression of nuclear factor κB, matrix metalloproteinase 9, and endoglin (CD105) in odontogenic keratocysts, dentigerous cysts, and radicular cysts

The aim of this study was to compare the immunohistochemical expression of nuclear factor κB (NF-κB), matrix metalloproteinase 9 (MMP-9), and CD105 in odontogenic keratocysts (OKCs), dentigerous cysts (DCs), and radicular cysts (RCs). Twenty cases of OKCs, 20 DCs, and 20 RCs were analyzed. A labeling index (LI), which expresses the percentage of NF-κB-stained nuclei, was calculated for the analysis of NF-κB expression. Expression of MMP-9 in the epithelium and in the capsule of each lesion was scored as 0 (<10% stained cells), 1 (10%-50% stained cells), or 2 (>50% stained cells). In addition, MMP-9 immunostaining was analyzed in endothelial cells of vessels with a conspicuous lumen. The angiogenic index was determined based on the number of anti-CD105 antibody-stained microvessels. In the epithelial component, the NF-κB LI was higher in OKCs than in DCs and RCs (P < .001). Analysis of MMP-9 expression in the epithelial component showed a predominance of score 2 in OKCs (90%), DCs (70%), and RCs (65%; P = .159). Evaluation of the NF-κB LI according to the expression of MMP-9 in the epithelial lining revealed no significant difference between lesions (P = .282). In the fibrous capsule, the highest percentage of MMP-9-stained cells (score 2) was observed in OKCs (P = .100). Analysis of the expression of MMP-9 in the vessels of odontogenic cysts showed a predominance of score 2 in OKCs (80%) and RCs (50%) and of score 1 in DCs (75%; P = .002). Mean microvessel count was high in RCs (16.9), followed by DCs (12.1) and OKCs (10.0; P = .163). No significant difference in microvessel count according to the expression of MMP-9 was observed between groups (P = .689). The results suggest that the more aggressive biologic behavior of OKCs is related to the higher expression of MMP-9 and NF-κB in those lesions. The differences in the biologic behavior of the lesions studied do not seem to be associated with the angiogenic index.

Expression of CD34 and CD105 as markers for angiogenesis in oral vascular malformations and pyogenic granulomas

The objective of this study was to assess angiogenic activity by analyzing anti-CD105 and anti-CD34 immunostaining in 20 cases of vascular malformations (VMs) and 20 cases of oral pyogenic granulomas (OPG). In addition, the usefulness of these markers for the differential diagnosis of these two oral tumors was evaluated. The results showed no significant difference in mean microvessel count between the anti-CD105 (P = 0.803) and anti-CD34 (P = 0.279) antibody. The mean number of vessels was 18.75 and 59.72 for oral VMs immunostained with anti-CD105 and anti-CD34 antibody, respectively, whereas in OPG the mean number was 20.22 and 48.09, respectively. CD34 was found to be more effective than CD105 in identifying blood vessels. However, the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this study supports the role of angiogenic factors in the etiopathogenesis of oral VMs and PG, but the results showed that quantification of angiogenesis cannot be used as a marker for the differential diagnosis of these two types of lesions.

Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium

The efficacy of mesenchymal stem cell (MSC) therapy for myocardial regeneration is limited by the poor survival of stem cells after transplantation into the infarcted heart. To improve the cell survival of MSCs in the infarcted heart, MSCs were genetically engineered to overexpress phosphoinositide-3-kinase class II alpha (PI3K-C2α). PI3K-C2α overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2α-MSCs. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2α-MSCs compared to hypoxic MSCs. Nine rats per group had 1 × 10 6 cells (20 μl PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2α-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2α-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2α-MSCs group as assessed using a Millar catheter at 3 weeks after transplantation. These findings suggest that overexpression of PI3K-C2α in MSCs can assist cell survival and enhance myocardial regeneration.

Mesenchymal Stem Cells Pretreated with Delivered Hph-1-Hsp70 Protein Are Protected from Hypoxia-Mediated Cell Death and Rescue Heart Functions from Myocardial Injury

Mesenchymal stem cell (MSC) therapy for myocardial injury has inherent limitations due to the poor viability of MSCs after cell transplantation. In this study, we directly delivered Hsp70, a protein with protective functions against stress, into MSCs, using the Hph-1 protein transduction domain ex vivo for high transfection efficiency and low cytotoxicity. Compared to control MSCs in in vitro hypoxic conditions, MSCs delivered with Hph-1-Hsp70 (Hph-1-Hsp70-MSCs) displayed higher viability and anti-apoptotic properties, including Bcl2 increase, reduction of Bax, JNK phosphorylation and caspase-3 activity. Hsp70 delivery also attenuated cellular ATP-depleting stress. Eight animals per group were used for in vivo experiments after occlusion of the left coronary artery. Transplantation of Hph-1-Hsp70-MSCs led to a decrease in the fibrotic heart area, and significantly reduced the apoptotic positive index by 19.5 +/- 2%, compared to no-treatment controls. Hph-1-Hsp70-MSCs were well-integrated into the infarcted host myocardium. The mean microvessel count per field in the infarcted myocardium of the Hph-1-Hsp70-MSC-treated group (122.1 +/- 13.5) increased relative to the MSC-treated group (75.9 +/- 10.4). By echocardiography, transplantation of Hph-1-Hsp70-MSCs resulted in additional increases in heart function, compared to the MSCs-transplanted group. Our results may help formulate better clinical strategies for in vivo MSC cell therapy for myocardial damage.

Evaluation of the clinical and immunohistological efficacy of the 585‐nm pulsed dye laser in the treatment of psoriasis

The 585-nm pulsed dye laser (PDL) therapy is useful for the patients with psoriasis. PDL treatment is based on selective photothermolysis of the dermal vasculature. The objectives of this study were to evaluate the clinical and immunohistological effects of PDL on psoriasis and to examine the association between psoriatic dermal vasculature and the clinical effects. Eleven patients with recalcitrant psoriasis were treated with 585-nm PDL. Biopsy specimens obtained before and after treatment were stained with CD31. All microvessels to the depth of 400 microm from the rete ridge were counted and the internal diameters were measured. The mean percent reduction of plaque severity score was 42. The mean microvessel count decreased significantly from 63 to 35.6 ( P < 0.001). There was a strong positive correlation between the plaque severity score and microvessel number ( P < 0.001) and a strong negative correlation between the microvessel count of an untreated area and degree of the change in the microvessel count after treatment (P = 0.005). The findings of this study suggest that PDL treatment improves psoriasis. Moreover, PDL treatment decreased the number of dermal papillary microvessels. Dermal papillary microvessels are important pathogenetic targets of psoriasis, and PDL therapy, which selectively targets superficial vessels, is therefore a valid therapeutic approach.

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to overexpress integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about three and twofold, respectively. ILK-MSCs demonstrated an increase of twofold in the ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. The adhesion rate of ILK-MSCs also had a 32.2% increase on the cardiac fibroblast-derived three-dimensional matrix and ILK-MSCs showed higher retention by about fourfold compared to unmodified MSCs. Six animals per group were used for the in vivo experiments analyzed at 1 week after occlusion of the left coronary artery. ILK-MSC transplanted rats had a 12.0% +/- 3.1% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 16.0% +/- 0.4% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by two-thirds when compared with ligation only. The mean microvessel count per field in the infarcted myocardium of ILK-MSCs group was increased relative to the sham group and MSCs group. In conclusion, the ILK gene transduction of MSCs further assisted cell survival and adhesion, and improved myocardial damage when compared with MSC only after transplantation.

Evaluation of colon cancer vascularity by flash echo imaging

Objective. Tumor vascularity is strongly related to the prognoses of patients with various malignant primary tumors, including colorectal cancer. The aim of this study was to confirm the usefulness of harmonic flash echo imaging (H-FEI) for the preoperative evaluation of tumor vascularity in colorectal cancer by comparison with CD34 staining of resected specimens. Material andmethods. Seventeen patients undergoing surgical resection for advanced colorectal cancer (9 M, 8 F) were enrolled in this study. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic) was used for H-FEI. After intravenous injection of ultrasonic contrast medium (SHU 508A), intermittent harmonic scanning was carried out for 120 s at intervals of 4 s. On the tumor image of the strongest enhancement in each patient, 5 regions of interest were taken to decide the mean echo intensity of the tumor. Immunohistochemistry using antibodies against CD34 was carried out on resected specimens. The mean microvessel density was decided by counting microvessels on 5 fields (×400) of CD34-stained specimens. Results. The mean value of H-FEI intensity was 5.44±1.10, and the mean microvessel count with CD34 staining was 35.0±7.95. A significant positive linear correlation was observed between the intensity of H-FEI determined preoperatively and the microvessel count in CD34-stained specimens (r=0.741, p=0.0006). Conclusion. Vascularity of colon cancer can be evaluated non-invasively using H-FEI.

Dickkopf‐3 As a New Potential Marker for Neoangiogenesis in Colorectal Cancer: Expression in Cancer Tissue and Adjacent Non‐Cancerous Tissue

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3.Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.

Angiogenesis in squamous precancerous cervical lesions

Vascularisation is one of basic tumor's characteristics. Neoangiogenesis starts at the stage of the dysplastic epithelial changes, thus before the progression into invasive lesion. This study was designed to determine the relation between stromal angiogenesis and the grade of cervical intraepithelial changes (CIN). The tissue sections of 50 cone biopsies were immunohistochemically stained for CD31 antigen, a marker for endothelial cells. All microvessels along the basement membrane subtending dysplastic epithelium were counted. The mean microvessel count was calculated from the three separate fields for each specimen. All the cases were devided into four groups: normal cervical epithelium (n = 5), CIN1 (n = 7), CIN2 (n = 13), and CIN3 (n = 25). The mean microvessel count (MVC) under the dysplastic epithelium was 18.1. For the patients with CIN1 changes the mean MVC was 12.9, while this number was 18.72 and 19.24 for the patients with CIN2 and CIN3 grade of epithelial changes, respectively. In a subset of the high grade lesions vascular structures were also noted in the upper layer of the epithelium. The mean MVC in the cases with the presence of these structures was 22, while this number was 12.91 in the cases without intraepithelial vessels. Althoug we found an increase of the mean MVC with the increase of the CIN grade, statisticaly significant differences were found out between CIN1 and CIN3 lesions. The mean MVC of the patients with the presence of intraepithelial vessels was statisticaly higher than the mean MVC of the patients without these structures. On the basis of the obtained results, we can conclude that the mean MVC and CIN grade positively correlated, while the number of cases with intraepithelial vessels increased with the CIN grade.

Expression of VEGF-C, VEGF-D and their receptor VEGFR-3 in diffuse large B-cell lymphomas

Lymphangiogenesis—the new growth of lymphatic vessels is an important route for the metastatic spread of human cancer. The receptor tyrosine kinase VEGFR-3 is expressed predominantly on lymphatic endothelium, and activation by its ligands VEGF-C and VEGF-D induces lymhpangiogenesis. VEGF-C, VEGF-D and VEGFR-3 have been found to play an important role in the lymphangiogenesis of several cancers. The present study investigated the expression of these factors by immunohistochemical staining of diagnosis specimens from 38 patients with diffuse large B-cell lymphoma (DLBCL). VEGF-C, VEGF-D and VEGFR-3 were expressed in both lymphoma cells and endothelial cells of blood and lymphatic tissue in all but one patient (who was negative for VEGF-D in lymphoma). There was a significant correlation in the intensity of staining between VEGF-C and -D in lymphoma and blood vessels (P < 0.001), and between the intensity of staining of VEGF-D and the patient International Prognostic Index score (P = 0.049) and borderline significance with overall survival (P = 0.051). Mean microvessel count was 58 (range 23 – 120), and it increased in association with high-intensity VEGF-C staining in lymphoma cells. Our findings indicate the importance of lymphangiogenic factors in the pathogenesis of DLBCL and suggest a potential therapeutic role for antilymphangiogenesis agents.

Expression of VEGF-C and Its Receptor VEGFR-3 in Diffuse Large B-Cell Lymphomas.

Vascular endothelial growth factor (VEGF)-C and its receptor tyrosine kinase VEGFR-3 are critical regulators of lymphangiogenesis. Their expression has been observed in a variety of solid tumors and was associated with lymph node metastasis in patients. The aim of this study was to evaluate whether aggressive lymphatic malignant cells express VEGF-C and its receptor VEGFR-3 and whether the expression correlates with intratumoral microvessel density, and patient outcome. Pathological specimens were taken at diagnosis from 29 diffuse large B-cell lymphoma (DLBCL) patients (11 men, 18 females, mean age 70 years) who were diagnosed between the years 1997–2001. The specimens were evaluated by immunohistochemical staining to determine the expression of VEGF-C and VEGFR-3 and the microvessel count (by factor-VIII-related antigen). All lymphoma specimens demonstrated positive staining for VEGF-C and VEGFR-3 with high intensity staining in 50% and 68% of the specimens respectively. The mean microvessel count was 58 (range 23–120) and blood vessels in all specimens demonstrating positive staining for both VEGF-C and VEGFR-3 (strong in 25% and 58% respectively). We found a significant correlation between high serum levels of β2 microglobulin and high VEGFR-3 staining. High intensity staining was found in 77% of the patients with high β2 microglobulin compared to 44% of the patients with normal β2 microglobulin level (p=0.03).The patients who expressed high intensity VEGFR-3 staining had worse survival. In the 13 patients who lived more than 5 years, only 46% of them demonstrated high intensity staining while 85% of patients that lived less than 5 years demonstrated such staining (p=0.01). The median event free survival (EFS) was 21 months. A significantly higher proportion of the patients with low EFS (lower than 21 months) demonstrated high intensity staining for VEGFR-3, (p=0.01)These results suggest that DLBCL tumors express both VEGF-C and its receptor (VEGFR-3) and that this signaling pathway may be associated with patient's prognosis. [Display omitted]

Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of women treated with tamoxifen

The aim of this study was to evaluate the effect of tamoxifen on angiogenesis induced in rabbit cornea by breast carcinoma from post-menopausal women. Thirteen post-menopausal women with operable, estrogen receptor-positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days prior to undergoing definitive surgery, participated in this study. Twenty-six virgin female New Zealand white rabbits, 3-4 months old, weighing approximately 2.5 kg each, were divided into two groups of 13 animals and received corneal implants of tumor either pre- or post-tamoxifen treatment. After 10 days, the animals were sacrificed, the region of the cornea between the tumor implant and the limbus was removed and quantification of angiogenesis was carried out by evaluating the entire hematoxylin-eosin stained slide, using a 10x objective lens (100x magnification). Student t-test was used in the statistical analysis of the data and statistical significance was established at P < 0.05. Mean microvessel count was 106.8 +/- 5.9 pre-tamoxifen treatment and 54 +/- 5.6 post-treatment. According to Student t-test, there was a significant reduction in mean microvessel density following treatment with tamoxifen (P < 0.001). Rabbit cornea proved to be an interesting experimental model for the quantification of angiogenesis. Tamoxifen, when administered for 30 days to post-menopausal women with breast cancer, significantly inhibited angiogenesis induced by tumor fragments in rabbit cornea.

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Objective The primary aim of this study was to evaluate the prognostic and predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian cancer; second aim was to perform a preliminary investigation of intratumoral microvessel density (IMD). Methods The influence on survival and response to treatment of several clinico-pathological features, including Hb, was analyzed in 72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of 25 of the 72 patients to compare three different endothelial markers: anti-FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary analysis of the prognostic and predictive value of IMD, and its relationship with Hb and other clinico-pathological features, was performed. Results Hb ≥ 12 g/dl was significantly associated with a better overall survival in univariate analysis ( P = 0.0181) and was the only independent prognostic variable in multivariate analysis ( P = 0.0160). Hb was directly related to progression-free survival ( P = 0.0240) and complete response to treatment ( P = 0.016). In the preliminary investigation of IMD, mean microvessel count did not show any significant difference among the three endothelial markers used, but anti-CD34 revealed a more consistent staining reaction. The relationship between IMD and complete response to treatment was found near to statistical significance ( P = 0.05); Hb and IMD were inversely related ( r = −0.47; P = 0.045). Conclusions Hb has a prognostic and predictive value in advanced ovarian cancer. In our preliminary study, which was performed on a limited number of patients, we found anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible predictive factor of complete response to treatment, and IMD and Hb to be inversely related.

Cutaneous lesions of secondary syphilis are highly angiogenic

Background: The role of angiogenesis in infectious processes is poorly studied. Some viruses have been linked to angiogenesis, but the role of bacteria and protozoa in inducing angiogenesis in chronic infections is poorly understood. Objectives: We examined the role of angiogenesis in syphilis, a common and often difficult-to-treat infectious disease, especially in the setting of HIV/AIDS. Method: Microvessel counts were performed on 27 paraffin-fixed sections of secondary syphilis by staining with monoclonal antibodies against CD31. In addition, immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF) to determine whether increased angiogenesis may be mediated, in part, through increased production of VEGF. Results: The CD31 mean microvessel count in secondary syphilis sections was significantly higher than in normal control sections. VEGF intensity appeared increased in the patients with secondary syphilis. Conclusions: Infection with Treponema pallidum results in increased angiogenesis in secondary syphilis. The mechanism for increased angiogenesis may involve elaboration of angiogenic cytokines, such as VEGF and epidermal growth factor. (J Am Acad Dermatol 2003;48:878-81.)

Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in angiogenesis of human cardiac myxoma.

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chemotactic protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among MCP-1 expression, TP expression, microvessel count (determined by CD31 staining), macrophage count (determined by CD68 staining), and the clinicopathologic features of the patients were analyzed statistically. Immunohistochemical analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in stromal cells such as infiltrating cells, fibroblast-like cells and endothelial cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all myxomas and occasionally in the endothelial cells. In the tumor stroma, the major source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. The proportions of MCP-1-positive myxoma and stromal cells significantly correlated with the proportion of TP-positive stromal cells. The mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or TP expression was significantly higher than that in myxomas with low tumor and low stromal MCP-1 or TP expression. Small tumors (< or =55 mm in diameter) exhibited high MCP-1 or TP expression, and the microvessel count in small tumors was significantly higher than in large myxomas. Although the difference was not significant, myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. These results indicate that in cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals accompanying growth.

Neovascularization in pancreatic ductal adenocarcinoma: Microvessel count analysis, comparison with non-cancerous regions and other types of carcinomas

Although neovascularization is regarded as an essential factor for tumor growth, it is unclear whether pancreatic adenocarcinoma is also influenced by this process. Furthermore, the reported microvessel count (MVC) data can not be compared due to the diversity of evaluating methods, and the relation between MVC data and metastatic potentials remains controversial. A total of 24 pancreatic adenocarcinomas and 24 adjacent non-cancerous pancreatic parenchyma were analyzed for MVC using anti-CD31 antibody. In addition, the MVC of 15 hypervascular tumors (10 hepatocellular carcinomas: HCC and 5 islet cell pancreatic tumors: ICT), 30 other types of adenocarcinomas (10 gastric, 10 colon and 10 intraductal papillary mucinous tumors of the pancreas: IPMT), as well as that of non-cancerous areas, were also analyzed. The extent of hepatic and peritoneal spread in 24 pancreatic adenocarcinoma patients was classified and correlations with MVC were evaluated. The mean MVC of 24 pancreatic adenocarcinomas (31.6 +/- 11.1) was actually lower than that of HCCs (91.6) or ICTs (56.4). The diversity is temperate as compared with that of other adenocarcinomas, i.e., 42.9 in gastric carcinomas, 35.6 in colon carcinomas and 32.5 in IPMT. MVC in non-cancerous areas were significantly higher in the pancreas (112.8) than in the stomach (29.6) or colon (26.3). MVC ratios of the cancerous area to the non-cancerous area were significantly lower in the pancreas (0.2818 +/- 0.100) than in the stomach (1.569 +/- 0.526, p<0.001) or the colon (1.423 +/- 0.493, p<0.001). MVC were higher in diffuse hepatic metastasis patients (36.0) than in limited metastasis patients (25.7). In conclusion, MVC in pancreatic adenocarcinoma revealed vascular volume to actually be lower than that of hypervascular tumors. We believe, however, that this hypovascularity is due mainly to contrast with the hyper-vascular non-cancerous pancreas, since MVC in the cancerous area itself was at the same level as in other adenocarcinomas. In addition, we revealed MVC to be of value for predicting the extent of liver metastasis.