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Background: Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs).Methods: Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis [vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)] by Real-time PCR.Results: Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05).Conclusions: These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Accelerative effect of topical administration of DEO on infected wound healing; (A) DEO by up-regulating the FGF-2 and VEGF expression enhances the angiogenesis and fibroblasts distribution, respectively. That in turn enhances the vascularization and cellularity at early stages of the healing process. On day 8 after wound induction (B) the DEO by up-regulating the ERα expression increases the bcl-2 mRNA level and protein biosynthesis, which reduces the p53 expression and biosynthesis. All these alterations result in accelerated fibroblast proliferation that finally elevates the collagen biosynthesis as well as dermal maturation. The elevated bcl-2 expression enhances the epithelial cells proliferation and ultimately shortens the re-epithelialization. Highlights • DEO , exerted antibacterial impact against MRS. • DEO , shortened inflammation and promoted cellularity. • DEO significantly up-regulated VGEF and FGF-2 expression. • DEO ameliorated bcl-2, p53 and caspase III expression. • DEO provoked angiogenesis by enhancing ERα expression. Abstract Medicinal plants are conventionally used for wound healing, but their action mechanisms are still unknown. The present study evaluated the effect of topical administration of ointment containing dill (Anethum graveolens) essential oil (DEO) in the management of apoptosis and cell proliferation during MRSA-infected experimentally induced wound healing process in BALB/c mice model. The GC-FID and GC-MS techniques were used to analyze chemical composition of the essential oil. The mice were randomly divided into four treatment groups including negative control (sham), 2% and 4% DEO and mupirocin®-treated animals. The full-thickness excisional wounds were inoculated by 5 × 107 colony-forming units of MRSA. In order to assess the effect of different concentrations of DEO on wounds infection, wound area, bacterial count, histopathological, immunohistochemical and RT-PCR analysis were evaluated. The GC-MS analysis identified α-phellandrene (47.3%), p -cymene (18.5%) and carvone (14.1%) as the main compounds of the essential oil tested here. Administration of DEO prevented bacterial growth and also reduced wound area in comparison to the control group. Topical administration of DEO significantly reduced the inflammatory phase and accelerated re-epithelialization, angiogenesis, fibroblast and collagen deposition. Moreover, the DEO-treated animals exhibited higher expressions of Bcl-2, p53 caspase-3, VEGF and FGF-2 in comparison to the control and mupirocin®-treated groups (P < 0.05). Topical administration of DEO decreases the inflammatory phase by increasing p53 and caspases-3 expression. It triggers the proliferative phase by up-regulation of the Bcl-2, VEGF and FGF-2 expression and also up-regulates the collagen biosynthesis by enhancing the ERα expression level. Thus, ointment prepared from dill essential oil, in Iran, with its major compounds such as α-phellandrene, p -cymene and carvone can be used as an agent for accelerating the infected wound healing. [ABSTRACT FROM AUTHOR]

Objective: Process of angiogenesis is essential for successful gestation. Disruption in this pathway leads to various undesirable consequences in pregnancy such as recurrent spontaneous abortion (RSA). One of the most important genes involved in angiogenesis is kinase-insert domain-containing receptor (KDR). This study aimed to investigate the associations between two single-nucleotide polymorphisms (SNPs) of KDR gene, 1719A > T and 1192G > A, with idiopathic RSA in south-east Iran.Methods: A total of 230 women, including 110 women with a history of at least two consecutive spontaneous miscarriages and 120 healthy women were recruited in this study. Genomic DNA was extracted from peripheral blood samples of participants using the Salting out method. The KDR 1719A > T and 1192G > A polymorphisms were genotyped by the standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique.Results: For the case group, frequencies of 2.73%, 30% and 67.27% were observed for AA, AT and TT genotypes in1719A > T SNP, respectively, and the genotype frequencies for controls were equal to AA = 3.33%, AT = 32.5% and TT = 64.17%. Distribution of genotypes in 1192G > A SNP in the case group was 79.1%, 19.1% and 1.8% for GG, AG and AA, respectively, whereas the corresponding values for the controls were GG  =  80%, AG  =  20% and AA  =  0. No significant difference was found between the case and control groups based on the frequency of KDR gene polymorphisms with the susceptibility to RSA.Conclusions: There is no association between these two SNPs of KDR gene and the susceptibility to RSA in women from south-east Iran. [ABSTRACT FROM AUTHOR]

Background Cynodon dactylon, a valuable medicinal plant, is widely used in Iranian folk medicine for the treatment of various cardiovascular diseases such as heart failure and atherosclerosis. Moreover, its anti-diabetic, anti-cancer and anti-microbial properties have been also reported. Concerning the critical role of angiogenesis in the incidence and progression of tumors and also its protective role in cardiovascular diseases, we investigated the effects of the aqueous extract prepared from the rhizomes of C. dactylon on vascular endothelial growth factor (VEGF) expressions in Human Umbilical Vein Endothelial Cells (HUVECs) and also on angiogenesis in carrageenan induced air-pouch model in rats. Methods In the air-pouch model, carrageenan was injected into an air-pouch on the back of the rats and following an IV injection of carmine red dye on day 6, granulation tissue was processed for the assessment of the dye content. Furthermore, in an in vitro study, angiogenic property of the extract was assessed through its effect on VEGF expression in HUVECs. Results Oral administration of 400 mg/kg/day of the extract significantly increased angiogenesis (p < 0.05) and markedly decreased neutrophil (p < 0.05) and total leukocyte infiltration (p < 0.001) into the granulation tissues. Moreover, the extract increased the expression of total VEGF in HUVECs at a concentration of (100 μl/ml). Conclusion The present study showed that the aqueous extract of C. dactylon promotes angiogenesis probably through stimulating VEGF expression. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Ameloblastoma is the most common odontogenic tumor which is slow-growing, locally invasive and exhibit specific biologic behavior and high recurrence rate. Likewise, odontogenic keratocyst is a developmental odontogenic cyst that has a high recurrence rate and aggressive behavior. There are limited studies considering the relationship between the angiogenesis factors and the biologic behavior of these lesions. Purpose: the aim of this study was to evaluate the mean density of vessels in odontogenic keratocysts and ameloblastoma and investigate its possible relationship with biological behavior of these lesions. Materials and Method: In this descriptive-analytic cross-sectional study, 40 cases, comprising 10 odontogenic keratocysts and 30 ameloblastomas (10 plexiform, 10 follicular, and 10 unicystic type) were selected and were stained immuno-histochemically with CD34 and CD105. The micro vessel density was assessed and compared in all groups. T- test for the independent samples' Oneway Anova, Wilcoxon test and Tukey tests were adopted for statistical analysis. Results: A statistically significant difference was observed in mean vascular density (MVD) between the odontogenic keratocyst and ameloblastoma groups concerning the CD105 and CD34 markers (p= 0.005, p= 0.000, respectively). The MVD was significantly higher in ameloblastomas than odontogenic keratocyst. MVD with CD34 was significantly higher than MVD with CD105 in ameloblastomas (p= 0.00). Conclusion: It can be suggested that angiogenesis might be one of the mechanisms that is more possible to contribute the aggressive biological behaviors in ameloblastoma rather than odontogenic keratocyst. [ABSTRACT FROM AUTHOR]

Background: Convolvulus arvensis L. (Convolvulaceae), bindweeds, is inhabitant to Iran and its proteoglycan mixture (PGM) has been reported to possess different biological activities. In the present study, we aimed to investigate different properties of PGM including anti-tumor, anti-angiogenesis and immunostimulatory activities. Methods: PGM was prepared from the roots of C. arvensis. Various cancer cell lines were treated with PGM and the cytotoxicity was assessed after 24 h of incubation using MTT assay. In addition, J774A.1 macrophages were stimulated with LPS (1 µg/mL) and then with PGM. Then, production of nitric oxide (NO) as a marker of inflammation was measured using Griess reagent. Moreover, PGM was subjected to cultivated Leishmania major promastigotes and leishmanicidal activity was determined using MTT assay. More importantly, human umbilical vein endothelial cells (HUVEC) cultured on matrigel basement matrix and tube formation after treatment with PGM was considered microscopically for the determination of angiogenesis. Results: Obtained results revealed that PGM significantly inhibited the formation of vascular-like tubes by HUVECs without any effect on their viability. Furthermore, PGM significantly exhibited leishmanicidal activity by the mechanism of suppressing L. major promastigotes developmental growth in vitro. However, PGM was shown to have no effect on the growth of cancer cells and production of NO by LPS-stimulated macrophages. Conclusions: The present study provides some new evidence on remarkable leishmanicidal and anti-angiogenic activities of PGM. These findings also afford the scientific basis for the use of C. arvensis as a candidate medicinal plant for further thoroughly phytochemical investigations toward discovering leishmanicidal and anti-angiogenic compounds. [ABSTRACT FROM AUTHOR]

Leishmaniasis has been identified as a significant disease in tropical and subtropical regions of the world, with Iran being one of the disease-endemic areas. Various treatments have been applied for this disease, and amphotericin B (Amp B) is the second line of treatment. Side effects of this drug have been reported in various organs. The present study investigated the effects of different types of Amp B on fetal organs using in silico and in vivo assays (chicken embryos). In vivo analysis was done by checking pathological changes, angiogenesis, and apoptosis alterations on eggs treated by Amp B and AmBisome. In silico approach was employed to predict the affinity of Amp B and AmBisome to the vascular endothelial growth factor A (VEGF-A), its receptor (KDR1), apoptotic-regulator proteins (Bcl-2-associated X protein (Bax), B-cell lymphoma (Bcl-2), and Caspase-8. The ADME-toxicity prediction reveals that AmBisome possesses a superior pharmacological effect to Amp B. The best result of all the dockings in the Molegro Virtual Docker (MVD) was obtained between Bax, Bcl-2, Caspase-8, KDR1, and VEGF-A targets. Due to the lower Egap (HOMO–LUMO) of AmBisome, the chemical reactivity of AmBisome was higher than that of Amp B. In vivo analysis showed that embryos that received Amp B exhibited less vascular density than AmBisome. Amp B alone significantly increased the expression of apoptosis and decreased angiogenesis genes compared to AmBisome. The histopathology analysis of the treated embryos showed a reduction in the blood vessel collapse and an increase in degenerative and apoptotic–necrotic changes in the embryonic tissues. Overall, the results suggest the potential benefits of AmBisome over Amp B, which might be a better treatment strategy to treat leishmaniasis during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis, which is required for embryonic development and many physiological events, plays crucial role in many pathological conditions such as tumor growth and metastasis. Recent studies indicate anticancer and antitumor properties of saffron against human cancers. Many processes are affected by Electromagnetic Field (EMF) and its effect on proliferation and gene expression were examined. In this experimental study, the synergic effects of saffron and EMF on VEGFR2 gene expression in MCF7 cells were investigated. Methods: Saffron was extracted using freeze dryer. MCF7 cells were grown in RPMI 1640 medium supplemented with 10% FBS and incubated at 37°C with 5% CO2. After 24 hr cells were treated with saffron extract at concentrations of 100, 200, 400 and 800 μg/ml. Forty eight hr after treatment all flasks were exposed with EMF (50 Hz, 0.004 T). Then total RNA was extracted and cDNA was synthetized using specific primer. Synthetized products were analyzed by Real Time PCR to determine expression level of VEGFR2. Data were analyzed by SPSS (ANOVA & Tukey). Results: Critical inhibitory effect on VEGFR2 gene expression was 20% at 400 μg/ml. Synergic use of EMF and saffron extract showed most reduction (38%) at 100 μg/ml. On the other hand synergic use of 200, 400 and 800 μg/ml saffron aqua extract and EMF decline noticeably the VEGFR2 level of gene expression to 29, 35 and 36%, respectively. EMF itself also reduced VEGFR2 up to 25% in comparison with control group which is remarkable at p<0.001. Conclusion: Results indicate a decrease in the expression of vascular endothelial growth factor receptor in the treated samples with saffron extract compared to control. This reduction in VEGFR2 level induced by synergic treatment of saffron and EMF which reveals induction of inhibitory effects of saffron on angiogenesis and could be also considered as a promising chemotherapeutic agent in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Electrical stimulation (ES) profoundly affects angiogenesis by modulating the production of angiogenic factors. We evaluated the effect of sensory (direct current, 600 microamperes) and motor (monophasic pulse current, 2.5 to 3 milliamperes, 300-microsecond pulse duration, 100 Hz) intensities of cathodal current on the release of fibroblastic growth factor-2 (FGF-2) at the wound site and also the biomechanical and histological properties of healed skin. Ninety-six male, Sprague-Dawley rats were randomly assigned into one control and two experimental groups. A full-thickness skin incision was made on the dorsal region of each animal. The experimental groups received 10 sessions of ES (sensory or motor) for 1 hour per day every other day. The results showed that FGF-2 levels in the sensory group were significantly greater than in the other groups on the third day. In the motor group, FGF-2 levels were significantly decreased compared with the control group. There were no significant differences between the normalized ultimate strength and stiffness in the groups, but they tended to be higher in the motor ES group. We conclude that the application of sensory ES during the early stage of wound healing may have a beneficial effect on wound healing by inducing the release of angiogenic factors and decreasing the duration of the inflammation phase. [ABSTRACT FROM AUTHOR]

Objective: The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML) has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF). Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML. Materials and Methods: We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR. Results: Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001). However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861). VEGF-A and VEGF-C expression were not able to predict clinical outcome. Conclusion: Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML. [ABSTRACT FROM AUTHOR]

Background: This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyper- plastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. Methods: Handred cases of invasive ductal carcinoma were ¡mmunohistochemically investigated for the presence of smooth muscle ac- tin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue. Results: There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P< 0.001 ). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P< 0.001). MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001 ) and DCIS (P < 0.001 ), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001 ). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P< 0.001). Conclusion: Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts in stroma of tumor; probably may be a worse prognostic factor and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression. [ABSTRACT FROM AUTHOR]

Background and purpose: Cardiovascular diseases are the most common causes of death in Iran as well as in the world. SDF-1α, as an effective chemokine for decreasing inflammation and injury, plays a role in angiogenesis. This study compares and evaluates serum level of this chemokine in healthy people and those with AMI (Acute Myocardial Infarction) regarding age and gender. Materials and methods: This case-control study was conducted on two groups: 63 patients and 63 healthy participants (the relatives of other patients in other wards). Blood samples were taken in the first 24h of admission in both groups, whereas in the case group another blood sample was taken in the seventh day after admission. Data were collected through taking history of the patients and Paraclinic. Serum level of SDF-1α was also measured in the participants. Results: Among the participants enrolled in each group, 79.4% were males and 20.6% were females. In the AMI group, 80.95% were admitted due to their first heart attack and 63.5% had Q wave MI at the time of discharge. There was no significant difference in the serum concentration of SDF-1α between control (33.58) and case (33.71) groups in the blood sample taken in the first 24 hours (p>0.05). However, a significant difference was observed between that of the first day blood sample taken from the control group and the seventh day sample of the case group (132.12, p<0.05). Conclusion: Our study showed that the concentration of SDF-1α increased during the first week after AMI. Therefore, SDF1-α can be effective in AMI as an anti inflammatory and angiogenetic chemokine. [ABSTRACT FROM AUTHOR]

Aims: Pterygium is caused by a type of angiogenesis process and Bevacizumab (Avastin) acts against all kinds of VEGF and inhibits angiogenesis. According to the anti-angiogenic effect of Avastin and the considerable recurrence of Pterygium after surgery as the treatment choice, this study was conducted to evaluate the effect of this medication on recurrent Pterygium. Materials & Methods: This single arm clinical trial study was performed on 17 recurrent Pterygium patients who referred to the ophthalmology clinic of one of Tehran military hospitals during November 2008 to March 2009 and were selected by simple sampling method. Symptoms, refraction, astigmatism, angiogenesis and Pterygium size were measured at the beginning, at the first week and 1 and 3 months after injection of 1.25 mg Avastin in Pterygium bed. Data was analyzed by SPSS 11.5 software using Wilcoxon and Chi-square tests. Results: Eye irritation (p=0.04) and Pterygium angiogenesis (p=0.001) significantly improved. No significant difference was observed in astigmatism, Pterygium size and the level of refraction (p>0.05). Conclusion: Avastin has significant effect on eye irritation and angiogenesis but has less effect on other symptoms; therefore, judgment about its efficacy on recurrent ptrygia needs further study. [ABSTRACT FROM AUTHOR]

The basic pathogenic step in the process of tumor growth, invasion and metastasis is tumor-induced angiogenesis. The aim of this study was to evaluate the angiogenesis in colorectal carcinoma by microvascular density (MVD) determination with IHC (immunohistochemistry) method and to determine if and how angiogenesis correlates with clinicopathologic parameters. Sixty two archival, paraffin embedded tissue samples of colorectal carcinoma from Omid Hospital (Mashhad, Islamic republic of Iran) were selected. Microvessels were identified immunohistochemically, using monoclonal CD34 antibody. Two investigators examined the microvessel density then the median value of MVD was determined and correlated with clinicopathologic parameters. Tumor-induced angiogenesis of colorectal carcinoma statistically correlated with histological tumor grade (P=0.000). There was no significant correlation between intratumoral microvessel density and sex and age of patients, localization, and stage and histologicalal tumor type (P > 0.1). Intratumoral microvessel density quantification in histologic specimens of colorectal carcinoma reflects the grade of tumors and may be a useful additional prognostic factor. [ABSTRACT FROM AUTHOR]

Background: Obesity is defined as a chronic disease, and is known as a public health problem in developed and developing countries. Several studies have shown the effects of anti-obesity of α-lactalbumin., Aim: This study was designed to investigate the effect of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric parameters, body composition and angiogenesis factor, sirtunin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in obese people under a weight loss regime., Methods: Obese people who meet the inclusion criteria are included. Participants are randomly divided into four groups (alpha-lipoic (1200 mg) +weight loss regime group; Faradic (three 1 hour sessions) + weight loss regime group; alpha-lipoic (1200 mg) + Faradic (three 1 hour sessions) + weight loss regime group; control group (1200 mg placebo) for 2 months. At the beginning and the end of the study, demographic information, dietary intake, anthropometric parameters, body composition and serum levels of the angiogenesis factor (sirtunin-1, PGC1α and nitric oxide) are measured., Conclusion: Recent studies reported the anti-obesity effects of alpha-lipoic acid. This study is novel, since a similar study has not yet been carried out. This study evaluates the effect of 600 mg of alpha-lipoic acid supplementation or having three sessions of 1 hour per week electrical isotonic contraction induced by Faradic for 2 months alone or in combination in obese people that are undergoing a weight loss regime., Trial Registration: Iran Clinical Trials Registry, ID: IRCT20131117015424N2. Registered 2018-04-02.

Introduction: Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM., Methods: We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive., Results: The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017)., Conclusion: We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.

Astrocytomas, the most prevalent primary brain tumors, can be divided by histology and malignancy levels into four following types: pilocytic astrocytoma (grade I), diffuse fibrillary astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). For high grade astrocytomas (grade III and grade IV), blood vessels formation is considered as the most important property. The distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptor type 2 (CB2) in blood vessels and tumor tissue of astrocytoma is still controversial. Asrocytoma tissues were collected from 45 patients under the condition of tumor-related neurosurgical operation. The expression of CB1 and CB2 receptors was assessed using immunofluorescence, quantitative real-time RT-PCR and western blotting. The results indicated an increased expression of CB1 receptors in tumor tissue. There was a significant difference in the mount of CB2 receptors in blood vessels. More was observed in the grade III and glioblastoma (grade IV) than astrocytoma of grade II and control. This study suggested that, the expression increase of cannabinoid receptors is an index for astrocytoma malignancy and can be targeted as a therapeutic approach for the inhibition of astrocytoma growth among patients.