Vascular Endothelial Growth Factor Immunoexpression Research Articles

Association of Vascular Endothelial Growth Factor (VEGF) in Salivary Gland Tumors

Aim: To identify the association of vascular endothelial growth factor (VEGF) immunoexpression in the progression of salivary gland tumor. Study design: Comparative cross-sectional study Place and duration of study: Department of Pathology, Peshawar Medical College. Duration of study was six months from date of approval. Methodology: Forty five specimen of salivary gland tumor were studied in which 30 were benign and 15 were malignant. The endpoint assessment included Hematoxylin & Eosin (H&E) and VEGF immunoexpression. Results: The association of VEGF expression with salivary gland tumor was statistical significant (P<0.05). Maximum 18 samples (benign: 13, malignant: 5) were shown to have strong expression, 24 (benign: 16, malignant: 8) were shown moderate expression. Whereas, small and no expression was found in 2 (benign: 0, malignant: 2) and 1 (benign: 1, malignant: 0) sample, respectively. Conclusion: Overexpression of VEGF in both malignant and benign salivary gland tumors might be associated to progress salivary gland tumors. Keywords Benign tumor, Warthin tumor, Adenoma, Salivary gland carcinoma, Vascular endothelial growth factor

Aflibercept suppresses ovarian hyperstimulation syndrome: an experimental study in rats.

In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.

Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat

ABSTRACT The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta’s sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11–12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Structural changes and neurotrophic factors upregulation in submandibular gland in a rat model of depression: proposed correlation with stress indicators during and after the relief of depression.

This study evaluated the structural changes, the immunohistochemical and gene expression of neurotrophic factors in submandibular gland in a rat model of depression, and their correlation with depression parameters during and after relief of depression by voluntary running. Forty-eight male Wistar rats were divided into control, control-exercise, depression, and depression-exercise groups. Depression was induced using forced swimming protocol, while the relief of depression was induced using the rat voluntary running wheels. The depressive state of rats was evaluated by measuring the immobility duration and the serum corticosterone level. The immune expression was evaluated by measuring the optical densities (ODs) using ImageJ software, and the gene expression levels were investigated. In the depression group, the convoluted ducts appeared dilated with numerous secretory granules. The number of PCNA-stained cells was significantly decreased in the depression group as compared to control group and then significantly increased in the depression-exercise group when compared to the depression group with a negative correlation to stress indicator. The ODs of immuno-expression for the brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) increased significantly in the depression group as compared to control group. Both BDNF and VEGF immuno-expression displayed positive correlation with the stress indicators. Both BDNF and VEGF gene expression results confirmed their immunohistochemical results. The findings of this study explored the role of submandibular gland in secreting neurotrophic factors and raise a flag for the possibility of using salivary secretions as dependable and easy parameter for estimation of chronic stressed patients.Mini AbstractThe submandibular gland neurotrophic factors immuno-expression can be used in estimating chronic depressive disorders as they are correlated with stress indicators during and after the relief of depression.

Association of Vascular Endothelial Growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) with Radiotherapy Response in High-Grade Sarcomas

Background: Sarcoma is a rare malignant aggressive tumor originating from mesenchymal elements. High-grade sarcoma has a poor prognosis. The mortality rate of high-grade sarcomas is 50–75%. Radiotherapy is needed in high-grade sarcoma. Radioresistance in the high-grade sarcoma is still common. Vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) are molecular markers that play a role in radioresistance. This study aimed to analyze the association of VEGF and mTOR with radiotherapy response in high-grade sarcoma. Method: This study was an analytic observational study with a cross-sectional design. The minimum samples based on Lameshow’s formula included 40 selected paraffin-embedded tissue blocks from biopsy high-grade sarcoma, consisting of 20 samples of radioresistance and 20 samples of radiosensitive. Immunohistochemistry staining for VEGF and mTOR were performed on all samples. Statistical analysis used the Chi-Square test. The significance of the data was obtained when p-value <0.05.Result: High immunoexpression of VEGF (OR = 17, p < 0.05) and mTOR in high-grade sarcoma showed a significant association with radiotherapy response (OR = 16, p < 0.05). The stepwise logistic regression analysis revealed that both VEGF and mTOR immunoexpression influenced radiotherapy response simultaneously. Conclusion: In this study, which used a minimum sample, it can be concluded that the higher VEGF and mTOR immunoexpression showed the higher radioresistance in high-grade sarcoma.

VEGF Immunoexpression in Endometrioid Endometrial Carcinomas.

Vascular endothelial growth factor (VEGF) is the most important stimulator of endometrial tumor angiogenesis, a mechanism that may be a therapeutic target in the context of an incidence and persistent mortality of endometrial endometrial carcinomas (EEC). In this study, VEGF immunoexpression was analyzed for 50 cases of EEC in relation to the histopathological parameters of tumor aggressiveness. High VEGF scores have been associated with the high grade and advanced stage of EEC, but unrelated to the depth of myometrial invasion, the pattern of tumor invasion, or vascular invasion. VEGF may be useful for assessing EEC aggression, but also for tumor angiogenic potential, which recommends it as a possible mark for specific antitumor therapy.

Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1ɑ) in lacrimal gland Adenoid cystic carcinoma: Correlation with clinical outcome

PurposeVEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. MethodsVEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. ResultsImmunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872–150.495; P = 0.012) was the most significant poor prognostic factor. ConclusionsThis study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.

Suppression of the inflammation and fibrosis in Asherman syndrome rat model by mesenchymal stem cells: histological and immunohistochemical studies.

Asherman syndrome (AS) is a symptomatic intrauterine adhesion caused by endometrial basal layer fibrosis as a result of either uterine cavity surgery or infection leading to many complications. There is a concern to repair the injured tissues by using bone marrow mesenchymal stem cells (BM-MSCs). We aimed in this study to develop an animal model of AS and evaluate the anti-inflammatory and anti-fibrotic effects of BM-MSCs in this model through histological, immunohistochemical, and morphometric studies. Forty-two adult female adult albino rats were divided into (i) donor group composed of 2 rats used for isolation and propagation of BM-MSCs, and (ii) experimental groups: 40 rats equally divided into 4 groups: GpI (control), GpII (AS model), GpIII (BM-MSCs-treated AS rats), GpIV (untreated AS rats). Histological staining and immunohistochemical (IHC) detection of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and nuclear factor-kappa beta (NF-kB) were performed. The results were evaluated by morphometric and statistical analysis. Significant endometrial thinning, fibrosis, and degeneration of the endometrial epithelium with a significant decrease in PCNA and VEGF immunoexpression and a significant increase in NF-kB immunoexpression were detected in GpII and GpIV groups. These changes were substantially reversed in BM-MSCs-treated animals. BM-MSCs treatment resulted in substantial improvement of intrauterine adhesion in the rat model of Asherman syndrome.

The protective effect of fenofibrate, triptorelin, and their combination against premature ovarian failure in rats.

Cyclophosphamide (CP) is a chemotherapy alkylating agent that causes a lot of side effects including premature ovarian failure (POF). This study aimed to evaluate the possible protective effect of fenofibrate (FEN) in CP-induced POF. Rats were randomly divided into five groups as follows: negative control, CP, triptorelin (TRI)-treated, FEN (FEN)-treated, and FEN + TRI-treated. Histological study, collagen area fraction, and immunoexpression of proliferating cell nuclear antigen (PCNA) were evaluated. Also, estrogen, anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and ovarian malondialdehyde (MDA), nitric oxide (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were measured. CP significantly reduced ovarian follicle count, as compared with the control group (1.00 ± 0.76 versus 7.75 ± 1.83, respectively). Meanwhile, FEN, either solely or in combination with TRI, significantly increased ovarian follicle count, as compared with the CP group (3.88 ± 0.83 and 5.75 ± 1.39, respectively). As compared with the control group, CP increased the levels of MDA, NOx, IL-10, TNF-α, FSH, LH, and collagen area fraction; however, levels of GSH, SOD, VEGF, AMH, estrogen, and PCNA immunoexpression were reduced with CP. Administration of FEN either solely or in combination with TRI showed significant improvement in all the parameters previously mentioned. FEN can protect the ovary from CP-induced side effects possibly through antioxidant and anti-inflammatory actions.

The Effect of EGF on VEGF expression on Submandibular Salivary Gland of Albino Rats Receiving Doxorubicin

Background: Vascular endothelial growth factor (VEGF) has two prominent biological effects of inducing mitogenesis and migration of vascular endothelial cells and to produce permeability on the microvasculature. Epidermal growth factor (EGF), known by its mitogenic activity on different types of cells, could induce the proliferation and differentiation of the epithelial cells and stimulate its regeneration. Doxorubicin (DXR) is a widely used anticancer drug and is one of most commonly used chemotherapeutic drugs, however it may cause some serious complications such as toxicity in various tissues in the body.Aims: The present study aims to investigate the effect of EGF on the VEGF immunoexpression in submandibular salivary gland tissue of rats receiving Doxorubicin (DXR).Methods and Material: 30 male Albino rats, two months old and weighing 200-250 gm body weight, were divided equally into three groups as follows: Group I (control group). Group II: rats received 20 mg/kg body weight DXR as a single intra peritoneal injection. Whereas, group III: rats received the same dose of DXR and on the next day they were injected intraperitoneally with EGF in a daily dose of 10μg/kg body weight for 7 consecutive days.Submandibular salivary glands were dissected out and processed for histological investigation and immunohistochemical localization of VEGF in the glandular tissue.Statistical analysis used: ANOVA was used to compare the mean area percentage of VEGF immunostaining among the specimens of different groups followed by Tukey’s Multiple Comparison Test.Results: VEGF expression in submandibular salivary glands of rats significantly decreased after DXR injection. However, daily intraperitoneal injections of EGF restored normal levels of VEGF expression in the glandular tissue.Conclusions: EGF preserved glandular architecture after DXR injection and consequently the immunohistochemical expression of VEGF in the glands to approximately the normal level.

The role of hesperidin on healing an incised wound in an experimentally induced diabetic adult male albino rats. Histological and Immunohistochemical Study

Background: Skin ulcers and poor healing are serious problems in diabetic patients. Products of citrus herbal are promising in new studies. Many benefits of hesperidin especially for cutaneous functions including skin healing have been demonstrated.Aim of the Study: The aim of this work was to evaluate the possible healing effect of hesperidin on diabetic skin injury in adult male albino rats.Materials and Methods: Forty adult male albino rats were randomly divided into four equal groups (10 rats, each). Group I: the control; group II: hesperidin; group III: untreated diabetic rats; and group IV, diabetic rats treated with hesperidin. Skin specimens were obtained and processed for histological study using Hematoxylin and Eosin (H & E), Mallory trichrome (M.T) and immunohistochemical study using vascular endothelial growth factor (VEGF) Electron microscopic examination was done. Morphometric measurements of epidermal thickness and area percentage of collagen fibers were carried out followed by statistical analysis.Results: The untreated diabetic group showed incomplete closure and scab covering proliferating epidermis. Another area of self- healed malformed skin revealed reepithelization with increased thickness of epidermis significantly. Epidermal cells showed loss of polarity and in between hyaline material. The underlying dermis revealed a significantly increased disorganized collagen fibers and massive inflammatory cells infiltration. Also, moderate VEGF immunoexpression was observed. Diabetic skin treated with hesperidin revealed complete closure of the wounds with thin apparently normal epidermis. The underlying dermis revealed normal amount of well-organized collagen fibers with few inflammatory cells infiltration and spaces between collagen fibers. Strong positive VEGF immunoexpression was observed reflecting enhanced angiogenesis.Conclusion: Diabetic skin injuries are healing badly in relatively prolonged time. Hesperidin can be used as an adjunctive or alternative agent in diabetic wound giving good cosmetic results.

Evaluation of Angiogenesis in Multiple Myeloma by VEGF Immunoexpression and Microvessel Density.

Background Multiple myeloma (MM) is a plasma cell disorder characterized by monoclonal proliferation of plasma cells in bone marrow. Plasmablastic MM is a morphologic subset of MM, containing ≥2% plasmablasts of all plasma cells. Methods The study included 30 consecutively diagnosed patients of MM (6 plasmablastic, 24 nonplasmablastic) over a span of 2 years. Angiogenesis in MM was assessed by analysis of vascular endothelial growth factor (VEGF) immunoexpression by plasma cells and microvessel density (MVD) using anti-CD34 antibody. CD34 and VEGF immunohistochemical staining was performed in all the 30 cases. Angiogenesis was studied in relation to plasmablastic morphology and clinical profile to determine if any correlation exists between these. Results The mean VEGF expression of 80.83 ± 7.36 in plasmablastic myeloma cases was significantly higher compared with a mean VEGF of 53.54 ±17.09 in nonplasmablastic cases. Most of the cases (66.6%) of plasmablastic myeloma exhibited strong (3+) VEGF expression. The difference in mean VEGF expression between plasmablastic and nonplasmablastic cases was found to be statistically significant ( p = 0.001). The mean MVD in plasmablastic cases was 44.8 ± 3.69, while in the nonplasmablastic category, the mean MVD was 23.7 ± 5.14, difference being statistically significant ( p < 0.05). Also, a positive correlation was found between VEGF expression and MVD. Conclusion A moderate/strong VEGF intensity and higher MVD were found in cases of plasmablastic MM, suggesting that a more aggressive histological disease may be associated with increased production of VEGF. This finding might be helpful to identify a subset of patients with adverse prognosis and to provide antiangiogenic therapy to improve their survival. However, studies comprising larger number of patients are required to bring out a statistical significance to further substantiate these findings.

Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations.

IntroductionChronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown.AimTo evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU.Material and methodsThe study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex- and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis.ResultsThere was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm2) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group (r = 0.82, p = 0.002).ConclusionsIncreased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development.

Von Hippel-Lindau Gene Mutations and Vascular Endothelial Growth Factor Immunoexpression in Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults representing about 3% of all newly diagnosed cancers in the United States. Clear cell RCC is the most common subtype (70-80%) of RCC. Clear cell RCC can be familial, but 95% of cases are sporadic resulting from the germline or acquired mutation of Von Hippel-Lindau (VHL) gene. VHL tumor suppressor gene functions as a down regulator of vascular endothelial growth factor (VEGF). Mutations of VHL gene result in overexpression of VEGF, neoangiogenesis and tumor metastasis. Nowadays, anti-VEGF targeted therapy is used for treating metastasis clear cell RCC. However, drug resistance occurs over time. VHL gene targeted therapy combined with anti-VEGF therapy should be considered and detection of VHL gene mutations status becomes essential in these cases. The present study was aimed to detect the VHL gene mutations status and VEGF immunoexpression in 62 clear cell RCC patients by conventional polymerase chain reaction and immunohistochemistry. Three primer pairs were used to detect the mutations of 3 exons in VHL gene. The positive cases for VHL exon 1 mutation, exon 2 mutation and exon 3 mutation were checked by 2% agarose gel electrophoresis. Tumor grading was done by Fuhrman nuclear grading system and staging was done by pathologic TNM staging system. Fifty cases (80.65%) were VHL gene mutation positive and 12 cases (19.35%) were negative. VHL gene mutations were significantly associated with histological grades (p=0.005). Out of 62 cases, 24 cases were weakly positive (1+) and 38 cases were strongly positive (2+) VEGF immuno-reactivity. There was statistically significant association between VEGF immunoexpression and histological grades of clear cell renal cell carcinoma (p=0.00) as well as tumor stage (p=0.01). It was also found that VEGF immunoexpression of clear cell RCC was significantly associated with VHL gene mutation positive tumours (p=0.00). These results can be helpful in further invention of molecular targeted therapy for drug-resistant clear cell RCC patients.

Vascularity and angiogenesis level correlations with the clinical behavior of the central and peripheral giant cell granulomas of the oral cavity

Purpose: The aim of the current study was to compare vascularity and angiogenic activity in peripheral and central giant cell granulomas (GCGs) of the jaws as reflected by vascular endothelial growth factor (VEGF). Patients and Method: 3 males and 7 females complaining of peripheral giant cell granuloma (PGCGs) and fifteen (5 males & ten females) with central giant cell granuloma (CGCGs) were selected to assess and compare the VEGF immunoexpression in multinucleated giantcells, and mononuclear surrounding stroma. Results: The expression levels of VEGF were greater in CGCGs compared to PGCGs and in aggressive CGCG more than non-aggressive. Conclusion: The vascularity and level of angiogenesis within aggressive CGCGs are higher than those in non-aggressive lesions. The stronger VEGF expression, the higher clinical behavior aggressiveness of the different giant cells granuloma lesions.

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English

Histopathological study with immunohistochemical expression of vascular endothelial growth factor in placentas of hyperglycemic and diabetic women.

AIMS AND OBJECTIVES:Spectrum of hyperglycemia in pregnancy includes gestational diabetes mellitus (GDM), mild hyperglycemia, and overt diabetes. Many authors have worked on morphological changes of the placenta in diabetes, but few studies have correlated histopathological changes with vascular endothelial growth factor (VEGF) immunoexpression. The aim of this study was to detect different histopathological changes in various groups of diabetic placentas and to correlate with VEGF immunoexpression.MATERIALS AND METHODS:Pregnant women were screened for diabetes. They were subsequently divided into normoglycemic (12 cases), GDM (33 cases), mild hyperglycemic (13 cases), and overt diabetes (18 cases). Placentas collected were subjected to histopathological examination. VEGF expressions were studied by immunohistochemistry.RESULTS:Overt diabetic placenta displayed villous immaturity (44.4%), villous edema (38.9%), chorangiosis (61.1%), fibrinoid substance deposition (38.9%), and Hofbauer cell hyperplasia in 44.4% cases. GDM placentas displayed villous immaturity (45.5%), villous edema (45.5%), chorangiosis (42.4%), and fibrinoid substance deposition in 75.6% cases. Mild hyperglycemic placentas displayed villous immaturity (38.5%), chorangiosis (61.5%), and fibrinoid substance deposition in 61.5% cases. VEGF immunoexpression in GDM placentas was absent in all placental components except syncytiotrophoblast. VEGF expression in overt diabetic placentas was increased in syncytiotrophoblast and capillary endothelium compared to normoglycemic placentas. Mild hyperglycemic placentas expressed similar VEGF expression in all components when compared to normoglycemic controls. However, it displayed weak expression in vessel endothelium.CONCLUSION:Histopathological changes in diabetic placentas might be a consequence of altered or abnormal VEGF expression in diabetic placentas. Pathogenesis and VEGF expression in GDM placentas are significantly different from overt diabetic placentas.

P53 and VEGF expression in human temporomandibular joint discs with internal derangement correlate with degeneration

Aim: Temporomandibular joint (TMJ) disorders are one of the most relevant causes of chronic facial pain and disability. During histopathological conditions biomolecular mechanisms occur inducing histologic changes of the tissue itself. Human Tumor Protein p53 and Vascular Endothelial Growth Factor are related with cell-cycle control, angiogenesis and both play a central role during inflammation. The purpose of the present research was to investigate the immunoexpression and immunolocalization of Human Tumor Protein p53 and Vascular Endothelial Growth Factor in temporomandibular joint discs of individuals with internal derangement with anterior disc displacement in order to gain insights into the apoptotic and angiogenetic processes in the three bands of articular discs with or without reduction and compare them to the histological degeneration score. Methods: Paraffin samples of eighteen displaced temporomandibular joint and four control discs were analyzed by immunohistochemistry for the above evaluations. Results: Data showed a strong Human Tumor Protein p53 and Vascular Endothelial Growth Factor immunoexpression in the anterior and intermediate disc areas and a weak immunoexpression in posterior area of anterior disc displacement with reduction patients while anterior disc displacement without reduction patients demonstrated a weak Human Tumor Protein p53 and Vascular Endothelial Growth Factor immunolabelling in the anterior and intermediate areas and a strong immunoexpression in posterior band. These immunoexpressions correlated with histological degeneration score. Conclusions: According to our results it can be assumed in that when the more histopathological changes in the disc are releaved, major levels of p53 and VEGF are produced.

Paricalcitol may improve oxidative DNA damage on experimentalamikacin-induced nephrotoxicity model

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n = 32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A + P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4 μg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A + P had lower mean fractional sodium excretion (p < 0.001) as well as higher creatinine clearance (p = 0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p = 0.035) and serum 8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p < 0.001) were significantly lower; superoxide dismutase (p = 0.024) and glutathione peroxidase (p = 0.007) activities of renal tissue were significantly higher in group A + P than in group A. The mean scores of tubular necrosis (p = 0.024), proteinaceous casts (p = 0.038), medullary congestion (p = 0.035), and VEGF immunoexpression (p = 0.018) were also lower in group A + P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.

Vascular endothelial growth factor immunoexpression is increased in malignant salivary gland tumors.

Salivary gland tumors (SGTs) consist of a heterogeneous group of lesions accounting for 3% to 10% of all head and neck neoplasms. Little is known about their angiogenic properties, and despite vascular endothelial growth factor (VEGF) has been previously studied in these lesions, further investigations are warranted to better determine its clinical and prognostic significance. In the current study, a total of 132 formalin-fixed, paraffin-embedded SGTs were organized in tissue microarray blocks and submitted to immunohistochemistry against VEGF protein. Slides were scanned and immunoreactions analyzed using Pixelcount V9 algorithm (Aperio Technologies Inc, Vista, CA, USA). Clinical and follow-up data were retrieved from patients' medical charts. Tumors included 50 cases of pleomorphic adenoma, 32 mucoepidermoid carcinomas, 30 adenocarcinomas not otherwise specified, and 20 adenoid cystic carcinomas. A slight male preponderance was found (1.1:1.0), with a mean age of 47.5 years. Parotid gland was the most affected location. Vascular endothelial growth factor expression was found in the cytoplasm of all cases analyzed with variable intensity, proving to be overexpressed in malignant tumors if compared with pleomorphic adenoma. A significant correlation of VEGF reactivity was found only with age, showing no further significant associations. Age and presence of paresthesia were the only features that predicted a lower specific survival rate under univariate and multivariate analyses. Log-rank test evidenced VEGF high expression as a potential determinant of reduced survival, although a statistical significance could not be reached. Hence, considering VEGF overexpression in malignant tumors and its potential association with a lower survival rate, this protein might be associated with SGTs pathogenesis and aggressiveness.