Immunohistochemical Expression Of Vascular Endothelial Growth Factor Research Articles

Vascular Endothelial Growth Factor in Colonic Cancer, Ulcerative Colitis and Colonic Adenoma: An Immunohistochemical Study

BACKGROUND: Colon cancer is one of the most common malignancies worldwide. Colonic adenoma and ulcerative colitis (UC) are important precancerous lesions. Vascular Endothelial Growth Factor (VEGF) is a well-known pro-angiogenic factor plays important role in physiologic and pathologic conditions and in neovascularization in cancer and hence becomes a potential target for anti-angiogenic cancer therapy.AIM: This study investigated VEGF immunohistochemical expression in colon cancer and its precancerous lesions. MATERIAL AND METHODS:Â Paraffin blocks from two hospitals were collected in a year: Colon cancer: 20 cases, colonic adenoma: 15 cases, UC: 15 cases and 5 controls from normal mucosa. VEGF was assessed immunohistochemically using a primary anti-VEGF antibody (VG1, Dako, Denemark).RESULTS: Median age was 49 years (range 31-52) in cancer, 40 years (range 31-52) in adenomas and 33 years (range 27-43) in UC. VEGF expression was negative in control, significantly strongly positive in 90% of colonic adenocarcinoma (p= 0.001), significantly positive in adenomas (p= 0.002) - the weak positivity significantly seen in mild dysplasia (p= 0.001) - and significantly positive in 73.3% of UC cases (p=0.022).CONCLUSION: The significant increase in positivity of VEGF in precancerous to cancerous lesions may point to its potential role in the pathogenesis and progression of colonic neoplasia.

Vascular endothelial growth factor mRNA levels as a biomarker for short-term N-butyl-N-(4-hydroxybutyl) nitrosamine-induced rat bladder carcinogenesis bioassay.

Generically, carcinogenic effects of chemicals in bladder carcinogenesis are judged by induction of papillary or nodular (PN) hyperplasia in rats given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 4 weeks and the test chemical for 22-28 weeks. However, upregulation of vascular endothelial growth factor (VEGF) begins early in rat BBN bladder carcinogenesis. To establish a short-term rat bladder carcinogenic bioassay, we analyzed the correlations between VEGF, VEGF mRNA and bladder lesions inductions at 10 and 26 weeks after BBN treatment. Six-week-old male Wistar (slc) rats were given 0.05% BBN for 4, 10 or 26 weeks. To avoid individual rat bias, the bladders were investigated by partial cystectomy at 10 weeks and total cystectomy at 26 weeks. After induction, PN hyperplasia and carcinoma in rats increased with the length of BBN treatment and immunohistochemical VEGF expression also increased following carcinogenesis, but the immunoreactivity of individual lesions was quite variable. Moreover, induction of PN hyperplasia at 10 weeks' BBN treatment was not significantly correlated with that at 26 weeks' treatment; thus, it was not possible to predict the carcinogenic effect due to the induction of PN hyperplasia at 26 weeks' BBN treatment by that at 10 weeks' treatment. However, VEGF mRNA levels of rat bladders at 10 weeks' BBN treatment revealed a strong significant correlation with the incidence of bladder lesions at 26 weeks' treatment. Here, we suggest that quantitative VEGF mRNA levels are a good biomarker for a short-term BBN-induced bioassay for rat bladder carcinogenesis.

Role of vascular endothelial growth factor, survivin, and inducible nitric oxide synthase expression in psoriasis: an immunohistochemical study

Background Psoriasis (PS) is a common chronic, relapsing, immune-mediated disease involving the skin and joints of genetically predisposing individuals. Despite numerous studies, the pathogenesis of PS has not been fully elucidated. However, many pathogenic theories have been suggested. There is much evidence that PS is a polygenic disease modified to expression by triggering factors. PS is characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes, lymphocyte infiltration consisting mostly of T lymphocytes, and various endothelial vascular changes in the dermal layer, such as angiogenesis, dilation, and high endothelial venule formation. Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis, causing aberrant angiogenesis and vascular leakage in the upper dermis; it may also contribute to keratinocyte proliferation and epidermal barrier homeostasis in PS. Inducible nitric oxide synthase (iNOS) was found to be expressed in the keratinocytes of psoriatic lesions; in addition, there is increased expression of iNOS-specific mRNA transcripts. Survivin upregulation in psoriatic lesion in comparison with normal skin was evident, suggesting its role in the pathogenesis of PS. The aim of this study was to investigate the immunohistochemical expression of VEGF, survivin, and iNOS in psoriatic skin and to detect their role in the pathogenesis of PS. Patients and methods This study was carried out on 20 patients with PS vulgaris. Immunohistochemical reactions were carried out using the streptavidin-biotin immunoperoxidase system in this study to detect the extent of expression of VEGF, survivin, and iNOS in each specimen of the skin biopsy. Results A strong VEGF expression through the epidermis (mean 46.4 ΁ 19.7) was observed. VEGF was significantly upregulated in psoriatic skin in comparison with normal healthy skin ( P P P Conclusion VEGF, survivin, and iNOS appeared to be important factors in the pathogenesis of PS.

Prognostic significance of VEGF immunohistochemical expression in oral cancer: a meta-analysis of the literature

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF protein overexpression with the clinical outcome in patients with oral cancer, but yielded conflicting results. Electronic databases updated to March 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with oral cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 17 studies (n = 1,207 patients) that evaluated the correlation between VEGF overexpression detected by immunohistochemistry and survival in patients with oral cancer. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (hazard ratio [HR] = 1.89; 95 % confidence interval [CI], 1.24-2.55) and disease-free survival (HR = 2.08; 95 % CI, 1.14-3.02) in patients with oral cancer: 1.77 (1.09-1.44) in oral squamous cell carcinoma (SCC) patients and 4.28 (1.35-7.21) in adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) of the salivary glands. No significant heterogeneity was observed among all studies. VEGF overexpression indicates a poor prognosis for patients with oral SCC, ACC, and MEC of the salivary glands.

Relationship between preoperative serum TSH levels and expression of VEGF in papillary thyroid carcinoma

Vascular endothelial growth factor (VEGF) stimulates angiogenesis, increases vascular permeability and seems to correlate to aggressiveness of tumors. Increased expression of VEGF has been observed in papillary thyroid carcinoma (PTC). Thyroid stimulating hormone (TSH) is the major thyroid hormone, but its relationship with VEGF has seldom been studied. Therefore, we explored whether the immunohistochemical expression of VEGF was related to the serum TSH level. VEGF expression was analyzed in 43 archived PTC specimens using immunohistochemistry, with adjacent normal thyroid tissues used as controls. Serum TSH was measured by immunoradiometric assay before surgery and correlated to VEGF expression. Positive VEGF expression was found in 90% of 43 PTC tissue specimens, but not in normal tissue. The serum TSH levels revealed a positive correlation with VEGF expression, R = 0.592 (P < 0.01). TSH is a major thyroid hormone. Whether TSH promotes the progression of PTC is not known but the serum TSH levels reveal a positive correlation with VEGF expression.

Modulation of angiogenic factor VEGF by DNA-hsp65 vaccination in a murine CNS tuberculosis model

Tuberculosis (TB) is a serious public health problem. Development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. Vascular endothelial growth factor (VEGF) is a potent activator of vascular permeability and angiogenesis. VEGF seems to participate in breakdown of the blood brain-barrier (BBB) in tuberculous meningitis (TBM), contributing to worsening of disease. Therefore, the objective here was to extent the characterization of our previously described murine model of central nervous system TB (CNS-TB) by describing the VEGF participation in the CNS disease, and suggesting a vaccination plan in mice. Plasmid encoding DNA protein antigen DNA-hsp65 has been described as a protector against TB infection and was used here to test its effectiveness in the prevention of VEGF production and TB disease. Vaccinated mice and its controls were injected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) in cerebellum. Four weeks after BCG injection, mice were perfused and brains were paraffin-embedded for VEGF expression analysis. We observed VEGF immunohistochemical expression in TBM and granulomas in non-vaccinated mice. The DNA-hsp65 treatment blocked the expression of VEGF in mice TBM. Therefore, our murine model indicated the VEGF participation in the physiopathology of CNS-TB and the potential prevention of the DNA-hsp65 in the disease progression.

Microvessel density and expression of vascular endothelial growth factor in clinically localized prostate cancer

Identifying biological differences between benign lesions and malignant prostatic cancer (PC) may facilitate precise indication for more aggressive post-operative treatment. Therefore, we examined immunohistochemically histological specimens from 140 PC patients treated with radical surgery. The mean age of the patients was 62.9 ±6.2 (range 49.0-77.0) years. There were 13 (9.3%) at pTNM stage 1, 78 (55.7%) at stage 2, 40 (28.6%) at stage 3 and 9 (6.4%) at stage 4. In the analysed group there were 75 (53.6%) well-differentiated, 53 (37.8 %) moderately differentiated and 12 (8.6%) poorly differentiated tumours. The mean pre-operative prostate-specific antigen (PSA) level was 9.9 ±0.5 ng/ml. Concentration of serum PSA was significantly increased with pTNM stage (p = 0.011), Gleason score (p = 0.011) and tumour grade (p = 0.003). In 34 (24.3%) tumours vascular endothelial growth factor (VEGF) expression was not shown. In the analysed group of tumours the mean percentage of positive VEGF cells was 14.8 ±1.4% and was not correlated with tumour grade (p = 0.648) or Gleason score (p = 0.697). However, significantly higher values for the protein were observed in pTNM 3 (p = 0.035) and pTNM 4 (P = 0.037) than in pTNM stage 1. In the whole series of tumours the mean microvessel density (MVD) was 97.5 ±2.4 /mm². A non-significant decrease in the number of microvessels was observed in the highest pathological tumour volume (P = 0.631), Gleason score (p = 0.368) and tumour grade (p = 0.233). Prostate-specific antigen level was not associated statistically with either MVD (p = 0.466) or VEGF expression (p = 0.188). There was also no correlation between the immunohistochemical expression of VEGF and MVD (p = 0.925).

Increased Angiogenesis-associated Poor Outcome in Acute Lymphoblastic Leukemia

Angiogenesis in solid tumors is important for tumor growth, invasion, and metastasis. However, angiogenesis plays also an important role in hematological malignancies. We have analyzed the expression of vascular endothelial growth factor (VEGF) in the leukemic blast cells and microvessel density (MVD) in the bone marrow biopsy samples of the patients with acute lymphoblastic leukemia (ALL). Bone marrow MVD of the patients with ALL was significantly higher compared with normal controls and complete remission (P<0.001), but slightly lower than in patients with relapsed ALL (P>0.05). The bone marrow blast VEGF expression was significantly higher in newly diagnosed ALL patients, with predominant strong VEGF expression as compared with complete remission patients (who had negative or weak VEGF expression) (P<0.05), whereas initial values were slightly lower than in relapsed patients. There was a strong positive correlation between VEGF expression and MVD at presentation of ALL. Stronger expression of VEGF on blast cells indicates shorter overall survival in ALL. Furthermore, initial values of MVD had positive correlation with overall survival and leukemia-free survival (P=0.024 and P=0.017, respectively). Our data suggest that increased angiogenesis (confirmed by immunohistochemical expression of VEGF in leukemic blasts), and MVD may play an important role in the pathophysiology of ALL with prognostic implications. Thus, targeting VEGF pathway may bring the new approach for ALL treatment-using antiangiogenic drugs and tyrosine kinase inhibitors in combination with standard chemotherapy regimens.

Immunohistochemical Evaluation of Vascular Endothelial Growth Factor (VEGF) in Splenic Hemangiomas and Hemangiosarcomas in Dogs

Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to evaluate the immunohistochemical expression of VEGF in 23 splenic hemangiosarcomas and 7 splenic hemangiomas in dogs. Blood tests performed previous to splenectomy were analysed for correlation with tumour VEGF expression. Results showed significantly higher VEGF expression in hemangiosarcomas than hemangiomas and lower hematocrit values and red cell count in dogs affected with malignant neoplasia (P < 0.05). These findings suggest the presence of high VEGF levels may be related to the malignant vascular proliferation seen in hemangiosarcomas.

Immunohistochemical expression of VEGF, HIF1-a, and PlGF in malignant melanomas and dysplastic nevi

We evaluated the role of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma angiogenesis and investigated their expression in dysplastic nevi, as potential melanoma precursors. In addition, we examined a possible correlation of VEGF expression with PlGF and HIF1-a. These factors were detected immunohistochemically in 95 melanomas of all types and stages and in 28 dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or control nevi. HIF1-a expression was more intense in melanocytes around necrotic areas but did not correlate with melanoma type, the Clark staging or the Breslow thickness. A strong positive association was detected between HIF1-a and VEGF expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in neoplastic cells of the controls. Its expression was more intense in melanomas, especially in nodular melanomas of elevated stage and thickness. PIGF was detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression did not correlate with melanoma staging nor thickness; however, it was more intense in superficial spreading melanomas, where a weak positive association between VEGF and PlGF was also detected. There was no association between HIF1-a and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a key role in melanoma progression; it activates VEGF secretion, which induces angiogenesis and metastasis. The role of PlGF seems to be limited.

Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer.

Background:The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.Methods:Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary loge hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ2 test for heterogeneity and its impact on the meta-analysis was assessed by the I2 statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.Results:Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18–1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38–0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48–0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43–0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96–1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61–1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80–2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.Conclusion:These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.

Association between bisphosphonates and jaw osteonecrosis: A study in Wistar rats

This work aimed at determining whether bisphosphonate therapy produces a sufficient condition for jaw osteonecrosis after tooth extraction. Rats were allocated into 3 groups: (1) 11 rats treated with alendronate, (2) 10 rats treated with zoledronic acid, and (3) 10 control rats. The animals were subjected to tooth extractions, and at the end of bisphosphonate therapy, they were humanely killed. Histologic sections of the surgical site were processed and analyzed. The zoledronic acid group showed higher incidences of osteonecrosis, inflammatory infiltrate, and microorganisms. There was no significant difference for epithelial or connective tissue, root fragments, vital bone, and positive staining for vascular endothelial growth factor (VEGF) among the groups. Zoledronic acid is associated with jaw osteonecrosis, whereas alendronate did not produce a condition sufficient for osteonecrosis after tooth extraction. Neither zoledronic acid nor alendronate was associated with a reduced immunohistochemical expression of VEGF in vital bone at the tooth extraction site.

Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer

For patients with epithelial ovarian cancer (EOC) cytoreduction, with a combination of taxane and platinum, is the standard of care. Despite this, approximately 50% of patients with advanced disease will relapse and moreover 15-20% of cases of EOC are resistant to platinum based chemotherapy. Vascular Endothelial Growth Factor (VEGF), an angiogenic factor, is associated with poor prognosis. This study was undertaken to examine whether there is an association between VEGF-A expression in the tumour of EOC patients and their response to platinum based chemotherapy. The study cohort consisted of 66 patients with advanced stage EOC (FIGO III-IV). Ovarian cancer tissue was analysed for VEGF-A expression immunohistochemically. Protein expression was measured and correlated, with platinum sensitivity and overall patient survival. Median age of patients was 53 years, 45 patients had platinum sensitive disease (68%), the remaining patients being platinum resistant (32%). Of the platinum resistant group, 18 (86%) patients had high VEGF score compared to only 1 (2%) with high VEGF score in the platinum sensitive group. Median survival was 11 months in the patient group with high VEGF score versus 32 months in that cohort with low VEGF score. VEGF expression was significantly inversely correlated with overall survival (P < 0.0001). We demonstrated that tumours of patients with platinum resistant EOC exhibit higher levels of VEGF expression compared to the platinum sensitive group. VEGF in EOC, may be of clinical and therapeutic relevance and suggests a role for first line anti-angiogenic therapy.

Vascular endothelial growth factor and vascular endothelial growth factor receptor‐2 tumor expression in patients with advanced laryngeal cancer after induction chemotherapy for organ preservation

Vascular endothelial growth factor (VEGF) expression seems to be associated with worse overall survival in patients with head and neck squamous cell carcinoma. The purposes of this study were to assess the prognostic values of the immunohistochemical expression of VEGF and vascular endothelial growth factor receptor-2 (VEGFR-2) in a cohort of patients with operable advanced laryngeal cancer who had been treated with induction chemotherapy. VEGF and VEGFR-2 expression in the malignant cells was quantified by an enzyme immunosorbent assay in a retrospective series. Fifty-nine patients were included in this study. We found moderate to high VEGF expression in 61% of patients and none to low expression in 39%. VEGFR-2 expression was moderate to high in 58% of patients and was none to low in 42%. The probability of a complete response to induction chemotherapy was significantly higher in patients with none to low VEGF expression (74% vs 40%; p = .02). VEGF expression seems to be a significant predictor of complete response to induction chemotherapy.

VEGF and nitric oxide synthase immunoexpression in Down’s syndrome amniotic fluid stem cells

It has been previously observed that the amniotic fluid obtained from Down's syndrome (DS) pregnancies showed lower levels of vascular endothelial growth factor (VEGF) and higher levels of nitric oxide (NO) with respect to the controls, suggesting the presence of an imbalance between placental vascularization and altered endothelial function. The aim of our study was to evaluate the immunohistochemical expression and localization of VEGF and nitric oxide synthase (NOS) isoforms in cultured amniotic fluid mesenchymal stem cells (AF-MSCs) isolated from normal euploid pregnancies and pregnancies complicated by trisomy 21. In addition, we measured the VEGF and NO content in cell culture supernatants to analyse their production by AF-MSCs. AF-MSCs were obtained from women with foetal DS and controls matched for age and gestation, and expanded in culture. The cells were then evaluated for the immunohistochemical expression of VEGF and NOS isoforms, as well as for the release of VEGF and NO. Our analyses showed that both the VEGF expression and production were significantly lower in DS-AF-MSCs with respect to the controls. As regards NOS, immunohistochemical expression of eNOS was significantly reduced in DS-AF-MSCs, whereas the nNOS and iNOS were similarly immunoexpressed in both groups of cells. Moreover, we observed that the NO content was significantly higher in medium derived by DS-AF-MSCs. Our study shows, for the first time, the differences between AF-MSCs isolated from control and trisomy 21 pregnancies and suggest an involvement of NO and VEGF in the physiopathological mechanisms associated with DS pregnancy.

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

BackgroundThe aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx.MethodsWe examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored.ResultsThe tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively).ConclusionsIncreased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.

Stage I colorectal carcinoma: VEGF immunohistochemical expression, microvessel density, and their correlation with clinical outcome

Tumor-node-metastasis (TNM) stage I colorectal cancer is commonly characterized by a good prognosis, with 5-year survival around 80-90%; nonetheless, it undergoes disease progression in a percentage of cases, although the causes of adverse clinical course still remain to be elucidated. In the present study, we analyzed and compared the immunohistochemical expression of the pro-angiogenic vascular endothelial growth factor (VEGF) as well as the microvessel density (MVD) in a series of 27 surgically resected colorectal carcinomas obtained from patients deceased because of disease progression and in a cohort of 25 colorectal cancers from patients still alive with no evidence of disease progression 5 years after the initial diagnosis. The prognostic value of VEGF expression and of MVD on the overall survival to colorectal cancer was investigated. A variable VEGF immunoexpression was demonstrated in all the analyzed cases. High VEGF expression was significantly more frequent among patients deceased of the disease. These patients also displayed significantly higher MVD counts in their cancer in comparison to the patients alive after 5 years from surgery. Moreover, both high VEGF expression and MVD appeared as significant negative prognostic markers related to a shorter overall survival to stage I colorectal carcinoma, with VEGF representing an independent variable at multivariate analysis. VEGF assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Canine Mammary Tumours

The histopathological and clinical aspects of canine mammary tumours (CMTs) have been widely studied, but the variation in the biological behaviour of these neoplasms hampers the identification of prognostic factors. Sustained angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of several growth factors including vascular endothelial growth factor (VEGF). The present study characterizes the relationship between immunohistochemical expression of VEGF and gross (e.g. size and tissue fixation) and microscopical (e.g. type, growth, necrosis, lymphoid infiltration, lymph node metastasis, histological grade and proliferation index) features of CMTs. Forty-eight benign and 64 malignant CMTs were evaluated. Statistical analysis failed to show a significant relationship between VEGF expression and the pathological features, suggesting that VEGF expression occurs in both benign and malignant tumours and is independent of histological type, proliferation, tissue invasion or local metastatic capacity.

Role of vascular endothelial growth factor in women with PCO and PCOS: a systematic review

The aim of this study was to investigate the strategic role of vascular endothelial growth factor (VEGF) in the pathophysiology of polycystic ovary syndrome (PCOS) and to critically review the published trials that have evaluated VEGF in women with PCOS. An electronic database search of Medline, Embase, Cinahl and Cochrane library was conducted. Studies were included if they evaluated VEGF either in the circulation or in granulosa lutein cell culture media in in-vitro laboratory studies of women with a polycystic ovary (PCO) or PCOS. Studies analysing immunohistochemical expression of VEGF in PCO were also included. This review concluded that VEGF may have a strategic role in the pathophysiology of PCOS and is the key mediator in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) in women undergoing assisted reproductive procedures. Its role is perhaps not singular and several other factors such as the bioavailability of its soluble receptor sFlt-1 and a multidisciplinary orchestration of other cytokines and growth factors may be involved in the pathophysiology of PCOS and OHSS.

Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide

Researches on stem cells bring promise to functional skin repair. In particular, it has been recently suggested that mesenchymal stem cells (MSCs) could positively affect cutaneous wound healing through differentiation and paracrine action. The molecular mechanisms are not clear, even if there is increasing evidence for an important action of nitric oxide (NO), probably mediated by the regulation of the gene encoding for vascular endothelial growth factor (VEGF). The aim of our study was to investigate the immunohistochemical expression of VEGF and nitric oxide synthase (NOS) isoforms in human skin-derived MSCs, as well as the production of VEGF and NO, because these cells are less well characterized than bone marrow MSCs. MSCs were obtained from skin biopsies of healthy adult patients undergoing cosmetic plastic surgery, expanded and characterized for specific surface antigens. The cells were then evaluated for the immunohistochemical expression of VEGF, and NOS isoforms, as well as for VEGF and NO secretion in cell culture medium. Our immunohistochemical analysis showed that proliferating MSCs derived from human skin exhibit VEGF expression at cytoplasmic level as well as cytosolic and nuclear localization of all the three isoforms of NOS, even if with different patterns. In addition, our data evidenced the release of both VEGF and NO in cell culture supernatants. In conclusion, our results suggest that a therapeutic approach based on the human skin-derived MSCs may have a positive effect in wound healing conditions, through their ability to provide VEGF and NO to the damaged area.