High Vascular Endothelial Growth Factor Expression Research Articles

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

HIF1A protein expression is correlated with clinical features in gastric cancer: an updated systematic review and meta-analysis

To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ2, I2, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81–3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61–3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44–2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45–2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46–3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02–2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06–1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38–2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79–3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.

In vitro protective effect of recombinant prominin-1 combined with microRNA-29b on N-methyl-D-aspartate-induced excitotoxicity in retinal ganglion cells.

To determine the in vitro protective effect of recombinant prominin-1 (Prominin-1)+microRNA-29b (P1M29) on N-methyl-D-aspartate (NMDA)-induced excitotoxicity in retinal ganglion cells (RGCs). RGC-5 cells were cultured, and NMDA-induced excitotoxicity at the range of 100-800 µmol/L was assessed using the MTT assay. NMDA (800 µmol/L) was selected as the appropriate concentration for preparing the cell model. To evaluate the protective effect of P1M29 on the cell model, Prominin-1 was added at the concentration of 1-6 ng/mL for 48h, and the cell survival was investigated with/without microRNA-29b. After obtaining the appropriate concentration and time of P1M29 at 48h, real-time polymerase chain reaction (PCR) was utilized to detect the relative mRNA expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β2. Western blot detection was applied to measure the phosphorylation levels of protein kinase B (AKT) and extracellular regulated protein kinases (ERK) in RGC-5 cells after treatment with Prominin-1. Apoptosis study of the cell model was conducted by flow cytometry for estimating the anti-apoptotic effect of P1M29. Immunofluorescence analysis was used to analyze the expression levels of VEGF and TGF-β2. MTT cytotoxicity assays demonstrated that P1M29 group had significantly higher cell survival rate than Prominin-1 group (P<0.05). Real-time PCR data indicated that the expression levels of VEGF were significantly increased in both Prominin-1 and P1M29 groups compared NMDA and microRNA-29b group (P<0.05), while TGF-β2 were significantly decreased in both microRNA-29b and P1M29 groups compared NMDA and Prominin-1 group (P<0.05). Western blot results showed that both Prominin-1 and P1M29 groups significantly increased the phosphorylation levels of AKT and ERK compared to NMDA and microRNA-29b groups (P<0.05). Flow cytometry analysis revealed that P1M29 could prevent RGC-5 cell apoptosis in the early stage of apoptosis, while immunofluorescence results showed that P1M29 group had higher expression of VEGF and lower expression of TGF-β2 with a stronger green fluorescence than NMDA group. Prominin-1 combined with microRNA-29b can provide a suitable therapeutic option for ameliorating NMDA-induced excitotoxicity in RGC-5 cells.

Mild exposure to fine particulate matter promotes angiogenesis in non-small cell lung carcinoma

Fine particulate matter (PM2.5) is associated with public health problems worldwide. Especially, PM2.5 induces epigenetic and microenvironmental changes in lung cancer. Angiogenesis is important for the development and growth of cancer and is mediated by angiogenic factors, including vascular endothelial growth factor. However, the effects of mild PM2.5 exposure on angiogenesis in lung cancer remain unclear. In this study, we examined angiogenic effects using relatively lower concentrations of PM2.5 than in other studies and found that PM2.5 increased angiogenic activities in both endothelial cells and non-small cell lung carcinoma cells. PM2.5 also promoted the growth and angiogenesis of lung cancer via the induction of hypoxia-inducible factor-1α (HIF-1α) in a xenograft mouse tumor model. Angiogenic factors, including vascular endothelial growth factor (VEGF), were highly expressed in lung cancer patients in countries with high PM2.5 levels in the atmosphere, and high expression of VEGF in lung cancer patients lowered the survival rate. Collectively, these results provide new insight into the mechanisms by which mild exposure to PM2.5 is involved in HIF-1α-mediated angiogenesis in lung cancer patients.

Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer.

Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression. We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually. The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression. This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

Reprogramming of VEGF-mediated extracellular matrix changes through autocrine signaling

ABSTRACT Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC), VEGF has been associated with increased invasion and metastasis, processes that require cancer cells to traverse through the extracellular matrix (ECM) and establish angiogenesis at distant sites. To further understand the role of VEGF in modifying the ECM, we characterized VEGF-mediated changes in the ECM of tumors derived from TNBC MDA-MB-231 cells engineered to overexpress VEGF. We established that increased VEGF expression by these cells resulted in tumors with reduced collagen 1 (Col1) fibers, fibronectin, and hyaluronan. Molecular characterization of tumors identified an increase of MMP1, uPAR, and LOX, and a decrease of MMP2, and ADAMTS1. α-SMA, a marker of cancer associated fibroblasts (CAFs), increased, and FAP-α, a marker of a subset of CAFs associated with immune suppression, decreased with VEGF overexpression. Analysis of human data from The Cancer Genome Atlas Program confirmed mRNA differences for several molecules when comparing TNBC with high and low VEGF expression. We additionally characterized enzymatic changes induced by VEGF overexpression in three different cancer cell lines that clearly identified autocrine-mediated changes, specifically uPAR, in these enzymes. Unlike the increase of Col1 fibers and fibronectin mediated by VEGF during wound healing, in the TNBC model, VEGF significantly reduced key protein components of the ECM. These results further expand our understanding of the role of VEGF in cancer progression and identify potential ECM-related targets to disrupt this progression.

Effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients: A retrospective case-control study.

Due to the complex pathological mechanism of acute cerebral infarction, the role of vascular endothelial growth factor (VEGF) on the disease is not clear. Therefore, a retrospective case-control study was performed to explore the effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients. A total of 100 patients with acute cerebral infarction admitted to our hospital from April 2021 to April 2022 were selected. Blood samples from all patients would be routinely collected to detect the expression of serum VEGF. Pearson chi-square, Spearman correlation and univariate Logistic regression were used to analyze the clinical data to explore the relationship between VEGF expression and basic information, stroke degree, quality of life, and prognosis of patients. To determine whether VEGF can provide relevant basis for the early prevention and prognostic treatment of acute cerebral infarction. And multivariate logistic regression was used to calculate the odds ratio between each variable and VEGF expression. Pearson chi-square test and Spearman correlation coefficient showed that sex, degree of stroke, limb convulsions, loss of consciousness, hemiplegia, aphasia, mental functioning score, overall quality of life score, and short-term prognosis were significantly correlated with VEGF expression in 100 patients. Univariate logistic regression was used to describe the ORs and 95% confidence interval of subjects at the univariate level, and the degree of stroke (OR = 83.333, P < 0.001), tic of limbs (OR = 26.316, P < 0.001), loss of consciousness (OR = 23.256, P < 0.001), hemiplegia (OR = 62.500, P < 0.001), aphasia (OR = 76.923, P < 0.001), mental functioning score (OR = 7.937, P < 0.001), overall quality of life score (OR = 5.464, P < 0.001), short-term prognosis (OR = 37.037, P < 0.001) was significantly correlated with the high expression of VEGF. The level of serum VEGF was positively correlated with neurological impairment degree and prognosis in patients with acute cerebral infarction, the more severe the degree of stroke and the worse the prognosis.

Association of CD10 and VEGF Expression with Tumour Characteristics and Treatment Response in Patients of Carcinoma BreastA Prospective Cohort Study

Introduction: Majority of breast cancer patients receive systemic therapy. This has led to an extensive search for effective factors to predict the outcome. Two such markers for breast cancer are Cluster of Differentiation 10 (CD10) and Vascular Endothelial Growth Factor (VEGF). There is limited data available in the literature to support these parameters in breast cancer patients, especially from the Indian subcontinent. Aim: To ascertain the association of pre-chemotherapy levels of CD10 and VEGF with tumour load in breast cancer and treatment response. Materials and Methods: A prospective cohort study was conducted in the Department of Surgery in collaboration with the Department of Pathology at Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India, from November 2015 to February 2017. A total of 39 patients with Locally Advanced Breast Cancer (LABC) were included in the study. Preoperative levels of CD10 and VEGF were estimated in large needle core biopsy specimens. Standard anthracycline based chemotherapy was given to all patients as a 21 days cycle for three cycles. All patients underwent modified radical mastectomy after Neoadjuvant Chemotherapy (NACT). Levels of CD10 and VEGF were estimated again in the mastectomy specimen. Increase/decrease or no change in VEGF and CD10 expression percentage was ascertained for each patient after systemic therapy. Variables that were studied in the present study were Tumour, Nodes, and Metastasis (TNM) staging of patient, expression of VEGF and CD10 in large needle core biopsy specimens and its association with tumour load, response to NACT and its association with CD10 and VEGF and histopathological characteristics like presence or absence of lymphovascular invasion oestrogen, progesterone and Human Epidermal Growth factor Receptor 2 (HER2)/neu receptor status. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 22.0. Association between two ordinal variables was established using Kruskal-Wallis test. A comparison of ordinal paired data was done using Wilcoxon signed-rank sum test. The p-value &lt;0.05 was taken as significant. Results: The mean age of study participants was 42.0±11.4 years. Increase in TNM staging lead to higher CD10 and VEGF expression (p-value&lt;0.05 and &lt;0.029, respectively). There was a significant reduction in CD10 and VEGF expression postchemotherapy (p-value&lt;0.05). CD10 expression was found higher in subjects with ER-negative status (22 patients) with p-value=0.014 and HER2/neu positive status (19 patients) with p-value=0.028. Subjects with HER2/neu positive status had higher VEGF expression (20 patients) with p-value=0.032. Conclusion: CD10 and VEGF can be used as independent markers for indicating poor prognosis and can be used as target for development of novel therapies in carcinoma breast.

Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.

To explore clinical features and prognostic value of vascular endothelial growth factor (VEGF), interleukin (IL) 8, IL-10, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and receptor-interacting protein-2 (RIP2) in diffuse large B-cell lymphoma (DLBCL). A total of 68 DLBCL patients admitted to the Affiliated Hospital of Hebei Engineering University from January 2017 to June 2021 were included in this retrospective analysis. Serum VEGF was detected by enzyme-linked immunosorbent assay, serum IL-8 and IL-10 were detected by chemiluminescent enzyme immunoassay, and expression of PIK3CA and RIP2 in tumors was detected by immunohistochemistry. The correlation between clinical features of DLBCL and tumor-related index were analyzed. Cox regression was conducted to explore risk factors and hazard ratio. The serum level or expressions of VEGF, IL-8, IL-10, and RIP2 were significantly elevated with the increase of Ann Arbor Stage, International Prognostic Index (IPI) scores, Eastern Cooperative Oncology Group (ECOG) scores, serum lactate dehydrogenase (LDH) level, and the number of extranodal sites (all P < 0.05). Beside, these serum indexes were significantly higher in patients with the presence of extranodal involvement and germinal center B-cell (GCB), but significantly lower in patients with the presence of bone marrow involvement (all P < 0.05). Cox regression analysis for overall survival revealed that high expression of VEGF, high level of serum IL-8, serum IL-10, and RIP2, Ann Arbor Stage (III-IV), number of extranodal sites (>1), serum LDH level (≥245 U/L), IPI scores (3-5), ECOG scores (≥2), and bone marrow involvement were independent risk factors for the prognosis of DLBCL patients (all P < 0.05). The serum levels of VEGF, IL-8, and IL-10, as well as the expression of RIP2 and PIK3CA in tumor tissues, were highly correlated to clinical features of DLBCL, and high expression level of these indexes may have adverse effects for the prognosis of DLBCL patients.

Anti-Inflammatory Effect of Channa micropeltes Extract in Angiogenesis of Diabetes Mellitus Wound Healing

OBJECTIVE: Channa micropeltes extract contains albumin and omega-6 which possess antioxidant and anti-inflammatory agents that can promote macrophages in the wound healing process associated with diabetes mellitus (DM). In this study, we analyzed Nuclear Factor kappa B (NF-κB) and Vascular Endothelial Growth Factor (VEGF) expression as well as neovascular cells in the inflammatory stage of DM wound healing. METHODS: The 24 males Rattus novergicus were divided into 3 groups that were 20% Channa micropeltes ointment (Group I), 10% Channa striata extract ointment (Group II), and placebo ointment as a control (Group III). Ointments were applied 3 times daily. RESULTS: The highest expression of NF-κB was observed in Group III on Day 4 (15.50 ± 2.38), and the lowest was in treatment of Group I and Group II on Day 8 (4.75 ± 0.96). The highest expression of VEGF was observed in Group I on Day 8 (14.75 ± 0.96), and the lowest was Group III on Day 4 (7.00 ± 1.41). The highest count of neovascular cells was observed in Group I on Day 8 (11.00 ± 2.16), and the lowest was in Group III on Day 4 (5.50 ± 0.58). CONCLUSIONS: Channa micropeltes has an anti-inflammatory effect by regulating NF-κB expression and elevating VEGF expression in the angiogenesis process of DM wound healing.

Treatment outcomes of injectable thermosensitive hydrogel containing bevacizumab in intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration (IDD) is a common musculoskeletal disease and its treatment remains a clinical challenge. It is characterised by reduced cell numbers and degeneration of the extracellular matrix (ECM). Nucleus pulposus (NP) cells play a crucial role in this process. The purpose of this study is to explore the role of bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, in the treatment of IDD through local drug delivery. High expression of VEGF was observed in degenerating human and rat IVDs. We demonstrated that MMP3 expression was decreased and COL II synthesis was promoted, when VEGF expression was inhibited by bevacizumab, thereby improving the degree of disc degeneration. Thus, these findings provide strong evidence that inhibition of VEGF expression by local delivery of bevacizumab is safe and effective in ameliorating disc degeneration in rats. The injectable thermosensitive PLGA-PEG-PLGA hydrogels loaded with bevacizumab is a potential therapeutic option for disc degeneration.

Effect of Recombinant Netrin-1 Protein Combined with Peripheral Blood Mesenchymal Stem Cells on Angiogenesis in Rats with Arteriosclerosis Obliterans.

This work was aimed to explore the effect of recombinant netrin-1 protein and peripheral blood mesenchymal stem cells (MSCs) on the angiogenesis ability of atherosclerosis. 28 Sprague Dawley (SD) rats were taken as research models. The arterial occlusion models were created by surgery and then divided into the saline control group (n =7), netrin-1 treatment group (n =7), MSCs treatment group (n =7), and netrin-1 + MSCs combined treatment group (n =7). The peripheral blood MSCs were extracted from the peritoneal cavity of diseased SD rats and cultured alone or in combination with netrin-1. The individually cultured MSCs and netrin-1 were locally injected into the ischemic tissues of SD rats. The Tarlov scoring was performed at the first, second, and third week of treatment, respectively. The expression of vascular endothelial growth factor (VEGF) was also measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the capillary density was measured by immunofluorescence staining. The mean maximum contractility of the gastrocnemius muscle in each group was determined in the third week after treatment. The Tarlov score of the netrin-1 + MSCs group was significantly higher than that of the control group (P < 0.05) at the second week. To the 4th week of treatment, the Tarlov score of the netrin-1 + MSCs group was highly increased compared to the netrin-1 group and the MSCs group (P < 0.05). The expression of VEGF in the treatment groups was greatly increased each week compared to the control group (P < 0.05). Compared with the netrin-1 and the MSCs groups, the VEGF was also notably increased in the netrin-1 + MSCs group (P <0.05). The capillary densities of the treatment groups were observably greater than that of the control group in the second and third weeks (P <0.05), while the capillary density in the netrin-1 + MSCs group was also significantly increased than those in the netrin-1 group and the MSCs group (P < 0.05). The mean maximum contractility of the netrin-1 + MSCs group was remarkably higher than that of the other groups (P < 0.05). The netrin-1 + MSCs group achieved the higher Tarlov score, higher VEGF expression, higher capillary density, and better muscle recovery than netrin-1 and MSCs treatments.

Changes in Expression of the Vascular Endothelial Growth Factor in the Kidneys of Diabetic Rats During Aging

Background. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in most developed countries. A number of specific factors may contribute to the onset and progression of diabetic nephropathy. One of those specific factors is vascular endothelial growth factor (VEGF). We studied the expression of VEGF in the kidneys of diabetic rats during aging. Methods. Male Sprague-Dawley rats were injected with 55mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control group). Kidneys were collected after 2 weeks, 2 months, 6 months and 12 months, and were analyzed in three different kidney structures: glomeruli, proximal (PCT) and distal convoluted tubules (DCT). Sections were stained immunohistochemically, using VEGF.Results. Significant differences in marker expression were observed after 2 months, with higher VEGF expression in diabetic rats. Positive VEGF cells were detected exclusively in the glomeruli of diabetic rats after 2 months. After 2 weeks of DM onset, high VEGF expression was demonstrated in the distal tubules of diabetic rats, as well as a complete absence of VEGF expression in the distal tubules of the control group. Conclusions. The major change in expression of VEGF occurs after 2 months of DM onset, particularly in the DTC, implying an early onset of pathophysiological changes in diabetic kidneys, which would usually occur with aging. These findings help to contribute to our understanding of changes associated with DN and guide towards potentially appropriate treatment modalities.Key words: diabetes mellitus, kidneys, nephropathy, VEGF

The Expression and Prognostic Significance of VEGF and CXCR4 in Gastric Cancer: Correlation with Angiogenesis, Lymphangiogenesis and Progression.

The cellular response to hypoxia includes the expression of hypoxia-inducible factor-1 (HIF-1) and its target genes: vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4). The aim of this study was to investigate the expression and prognostic significance of VEGF and CXCR4, which are responsible for angiogenesis and progression in gastric cancer. Twenty-eight gastric cancer patients were analyzed. The mRNA expression was examined in primary tumors and corresponding normal gastric mucosa by RT-PCR. The protein level was examined by immunohistochemistry staining. The high expression of VEGF and CXCR4 was found in 71.0 and 64.0% of tumors, respectively. The mean levels of VEGF and CXCR4 were upregulated in primary tumors compared to normal mucosa (p = 0.0007, p = 0.0052). A correlation between VEGF expression and tumor invasion (p = 0.0216) and stage (p = 0.0181) was found. CXCR4 expression correlated with lymph node metastases (p = 0.0237) and stage (p = 0.0054). The VEGF expression correlated with microvessel density (MVD) (p = 0.0491). The overall 3-year survival rate was 46.4% and correlated negatively with high CXCR4 mRNA expression (p = 0.0089). VEGF and CXCR4 play an important role in tumor progression. Their overexpression correlates with a bad prognosis and may improve high-risk patient selection, and these patients may obtain additional survival benefits if treated more aggressively.

P-681 Balance of Estrogen:Androgen ratio (Estradiol E2: Dehydroepiandrosterone-sulphate DHEAS) and its symbiotic correlationship with Vascular-Endothelial Growth-Factor (VEGF) critically foments implantation and pregnancy outcomes in IVF cycles

Abstract Study question Is the estrogen/androgen balance vital for implantation and does this E2:DHEAS ratio coordinate with neoangiogenesis/neovascularisation (VEGF) to facilitate establishment of viable pregnancy in IVF cycles? Summary answer The Estradiol E2:DHEAS ratio independently as well as in symbiotic correlationship with VEGF is strongly predictive of invasive implantation and pregnancy outcomes in IVF cycles What is known already Decidualization of endometrial stroma and vascularization at feto-maternal interface is necessary for implantation. Estrogen Estradiol E2 is among the factors widely known to regulate these processes. Androgen Dehydroepiandrosterone (DHEA) is the designated primary precursor for natural estrogens. DHEA-induced PCOS mice have demonstrated adverse impacts on Embryo implantation and decidualization. However, role of DHEA/S in human implantation has not yet been explored. Vascular-Endothelial growth-factor (VEGF) is known to influence vascularization, angiogenesis, endometrial receptivity. Higher VEGF expression in endometrium is associated with pregnancy. However endometrial-biopsy for VEGF estimation is an invasive method for implantation studies and cannot be applied to ongoing cycles. Study design, size, duration Prospective study of n = 235 (Power of study&amp;gt;85%) non-PCOS, normal-responder infertile females (mean age 31.77±2.42 years, BMI 24.4±4.1, W/H ratio 0.82±0.07) undergoing fresh IVF treatment cycles using standard antagonist stimulation protocol at our fertility clinic during January 2019-December 2020. Elderly women (age&amp;gt;35 years), women with polycystic-ovaries, endometriosis and frozen-thawed cycles were excluded.7 cycles were cancelled owing to no embryo transfer (ET). Day3-cleavage stage or day5-blastocyst stage embryos were transferred (n = 228). Luteal-phase was supported with Micronized progesterone. Participants/materials, setting, methods Serum levels of Estradiol E2 and DHEAS were measured by Radio-Immunoassay and VEGF estimation by ELISA on day ET, day7, day14 post ET. Cycles were divided into Pregnant (P:n=73) and Non-Pregnant (NP=n=155) groups. Main outcome measures: Clinical Pregnancy (CPR:n=70=30.70%), Live-Birth (LBR:28.94%) rates. Secondary outcome measures: Biochemical-pregnancy (BCP:n=3=1.31%), Early-Miscarriage (EM:n=4=1.75%) rates. Pregnant=Serum βhCG&amp;gt;50 on d14ET. BCP=No exponential rise/tapering βhCG levels post d14ET, CP=positive cardiac activity at 6-8 weeks gestation, EM=non-viable intra-uterine pregnancy upto 12 weeks gestation. Main results and the role of chance dET: E2 did not differ significantly (780±50 vs. 750±30 pg/ml;p=0.61) whereas DHEAS = (212±11 vs. 170±6 ng/dL;p=0.0005), E2:DHEAS = (3.72±0.13 vs. 4.65±0.17;p=0.0011), VEGF = (658±20 vs. 495±16;p&amp;lt;0.0001) differed significantly between P vs. NP groups; indicating importance of E2/DHEAS ratio. D7ET: E2 = (790±57 vs. 222±19;p&amp;lt;0.0001), DHEAS = (381±28 vs. 1262±70;p&amp;lt;0.0001), E2:DHEAS = (2.37±0.25 vs. 0.30±0.029;p&amp;lt;0.0001), VEGF = (636±23.61 vs. 480±10.13;p&amp;lt;0.0001) displayed statistically robust differences between P vs. NP groups. d14ET: E2 = (855±73.45 vs. 193.2±13.31;p&amp;lt;0.0001), VEGF = (544.2±15.80 vs. 452.3±16.77;p=0.0011) displayed statistically robust differences between P vs. NP groups. Interestingly, although DHEAS = (685±41.05 vs. 806±55.37;p=0.18) did not differ significantly, E2:DHEAS = (1.643±0.26 vs. 0.45±0.048;p&amp;lt;0.0001) showed highly significant difference; again highlighting importance of E2/DHEAS balance. Ratio E2:DHEAS on d7ET correlated strongly with d7VEGF (Pearson r = 0.31,p&amp;lt;0.0001). ROC curve for d7 E2:DHEAS had AUC 78%, p &amp;lt; 0.0001 Hormone values and their rising trends (d/ET to d7/ET to d14/ET) varied with pregnancy outcome status E2= LB:(d/ET:780±50 to d7/ET:790±57 to d14/ET:855±73.45) vs. BCP:(d/ET:723.3±157.6 to d7/ET:743.3±159 to d14/ET:770±153) vs. EM:(d/ET:906.3±104 to d7/ET:1150±113 to d14/ET:1758±127) DHEAS= LB:(d/ET:212±11 to d7/ET:381±28 to d14/ET:685±41.05) vs. BCP:(d/ET:248.3±55 to d7/ET:266.7±71.2 to d14/ET:400±120.3) vs. EM:(d/ET:243.8±27 to d7/ET:303.8±11.43 to d14/ET:391.3±49) E2:DHEAS= LB:(d/ET:3.72±0.13 to d7/ET:2.37±0.25 to d14/ET:1.643±0.26) vs. BCP:(d/ET:2.93±0.15 to d7/ET:2.97±0.4 to d14/ET:2.12±0.32) vs. EM:(d/ET:3.78±0.40 to d7/ET:3.77±0.26 to d14/ET:4.68±0.59) Decreasing E2:DHEAS ratio (d/ET-d7/ET-d14/ET) is vital for successful implantation/Live-birth VEGF= LB:(d/ET:658±20 to d7/ET:636±23.61 to d14/ET:544.2±15.80) vs. BCP:(d/ET:513.3±37.56 to d7/ET:628.3±40.45 to d14/ET:468.3±35.63) vs. EM:(d/ET:647.5±78.8 to d7/ET:887.5±60 to d14/ET:1138±94.4) Limitations, reasons for caution This study is limited by small sample size and is not a randomized controlled trial. We have taken only representative molecules into consideration. There is a plethora of factors involved during the implantation process. Multi-centric systematic studies are needed to corroborate these findings and account for the probable confounding factors. Wider implications of the findings This novel study explores and highlights significance of maintenance of a critical estrogen/androgen ratio (E2:DHEAS), rather than individual estrogen or androgen markers, in the implantation process. We have also underscored how this ratio coordinates symbiotically with VEGF as a critical non-invasive determinant of implantation and pregnancy-outcomes in ongoing IVF cycles. Trial registration number Not Applicable

Does VEGF Expression Correlate with Lymphatic Metastasis in Breast Cancer?

IntroductionPrimary tumor characteristics are increasingly used for prognostication, predicting lymph node metastasis and planning adjuvant treatment in breast cancer. Vascular Endothelial Growth factor (VEGF) has been postulated to stimulate lymph vessels development and growth in tumors. Few studies on cell lines have documented how the new lymphatics develop or tumor cells invade these lymphatics. However, in human breast cancer the literature is sparse. Hence, this study is done to see the expression of VEGF and its correlation with lymphatic invasion in breast cancer patients.Materials &amp; MethodsFormalin fixed paraffin embedded blocks of breast cancer specimens and controls were retrieved &amp; 4u thick sections stained with H&amp;E stains for morphological evaluation. Serial sections were cut on APES (3‐Triethoxysilylpropylamine) coated slides for performing immunohistochemistry using monoclonal antibodies against VEGF and DII40. The expression intensity of VEGF and its distribution in the tumor samples were observed and semi‐quantitatively analyzed. VEGF expression was interpreted as follows: negative (0): &lt;5% staining; weak (+): 5–25% staining; positive (++): 26–50% staining; strongly positive (+++): &gt;50% staining. Statistical analysis: samples with 0/+ staining were considered in low VEGF expression, while samples with ++/+++ expression were considered as high VEGF expression. For DII40 well demarcated vessels showing positivity in endothelial cells were counted per 10hpf after selecting hot spots at scanner view. For statistical analysis, 0 was considered as no expression and 1/10HPF was considered as high expression. Association between levels of VEGF and D II 40 was examined by the two‐way scatter plot and a linear regression analysis of DII 40 over VEGF. The association of positivity between the two markers was assessed using Chi Square test.ResultsHigh VEGF expression was seen 33 of the 43 evaluable patients (76.74%%; 95% CI 61.37%‐88.24%) and high DII 40 expression was seen in 30 of the 44 patients (68.18%; 95% CI 52.42%‐81.39%). Of the 33 patients with high VEGF expression, DII 40 was expressed in 26 of them (78.79%). There was a strong association between VEGF expression and DII 40 expression (p&lt;0.01) (Figure 1). The variance explained by VEGF level in the variance of DII 40 as measured by the correlation (R2) was 0.1265 (p=0.02). When the expression of VEGF and D II 40 was compared with tumor characteristics, there was statistically significant correlation with lymphovascular invasion (LVI) but not with tumor size, type, grade, ER/PR status, Her2neu status or lymph node involvement.ConclusionVEGF expression is high in most tumors. There is significant association between LVI &amp; lymph vessels detection as studied by D II 40 expression and VEGF expression. Further studies in clinical settings are essential before incorporating VEGF expression for prognostication and customized patient care.

Multiwalled carbon nanotubes functionalized bacterial cellulose as an efficient healing material for diabetic wounds

The unique pool of features makes bacterial cellulose (BC) a robust platform to tailor its functionalities. Herein, the BC matrix was reinforced with multiwalled carbon nanotubes (MWCNT) to control infection and accelerate the healing process of diabetic wounds. The prepared BC-MWCNT composite film was characterized and antibacterial activity was assessed. Further, the in-vivo wound healing activity was performed and temporal expression of interleukin (IL-1α), tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF) and platelets derived growth factor (PDGF) was quantitatively measured by real-time PCR. The characterization results confirmed the reinforcement of the BC matrix with MWCNT. The composite film showed antibacterial activity against all the tested strains. Moreover, the macroscopic analysis of the wound demonstrated faster closure of the diabetic wound in BC-MWCNT group (99% healing) as compared to negative control (77%) in 21 days. Histological studies further supported the results where complete reepithelization of the epidermis and healthy granulation tissue were observed in BC-MWCNT treated group. Molecular studies revealed that BC-MWCNT group showed relatively lesser expression of pro-inflammatory cytokines IL-1α and TNF-α and higher expression of VEGF than control that may have favored the faster healing. This study suggested that the tailorable properties of BC can be exploited to develop composites with potential applications in diabetic wound healing.

Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer.

Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC). Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score. Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p < 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively). Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.

The Association of VEGF Expression with Degree of Differentiation and Lymphovascular Invasion in Colorectal Adenocarcinoma

BackgroundColorectal carcinoma is the third most common malignancy in the world. Colorectal carcinoma is a heterogeneous tumor withdifferent clinical pathologic features and prognostic values. For the same tumor-stage, patients could have difference prognosis andit has been suggested that the angiogenesis might be correlated with the prognosis, especially expression of vascular endothelialgrowth factor (VEGF) as the main pro-angiogenic factor. High VEGF expression in colorectal adenocarcinoma is associated withincreased blood vessels in invasive tumor area, cell proliferation and metastases. However, relation VEGF expression with thedegree of differentiation and lymphovascular invasion is not known.MethodsThis was a retrospective observational study with cross sectional approach. Samples were obtained from 39 paraffin blocks withdiagnosis adenocarcinoma not otherwise specific (NOS) in four Anatomical Pathology Laboratory in West Sumatera 2018 andevaluated for degree of differentiation and lymphovascular invasion. VEGF expressions in tumor cell were analyzed usingimmunohistochemistry staining. Bivariate statistical analysis used Fisher's Exact test and value p&lt;0.05 was considered significant.ResultsColorectal adenocarcinoma with high grade differentiation entirely had high VEGF expression (100%), while low gradedifferantiation with high VEGF expression was 60.7%. Lymphovascular invasion positive was mostly found with high VEGFexpression (80.6%). Statistical analysis showed significant association between VEGF expression with degree of differentiation(p=0.017) and lymphovascular invasion (p=0.028).ConclusionThe conclusion was VEGF expression had significant association with degree of differentiation and lymphovascular invasion ofcolorectal adenocarcinoma.

The study of immunohistochemical expression of vascular endothelial growth factor in renal-cell carcinoma

ObjectiveTo study immunohistochemical expression of vascular endothelial growth factor (VEGF) renal-cell carcinoma (RCC) and correlate its expression with the studied clinicopathologic parameters.BackgroundRCC is the sixth diagnosed cancer in males and the tenth in females accounting for 5 and 3% of cancer incidence, respectively. VEGF is a peptide with angiogenic properties. It is thought to have an important role in RCC development and progression.Patients and methodsThis retrospective study was performed on 58 cases of RCC and 31 cases of nonneoplastic kidney tissue. The slides were subjected to VEGF immunohistochemical staining using a streptavidin–biotin–peroxidase technique. The relationships between VEGF expression in RCC cases and nonneoplastic cases, as well as correlation between VEGF expression and clinicopathological parameters in RCC cases, were statistically analyzed.ResultsVEGF showed low expression in 27.6% and high expression in 72.4% of RCC cases versus 48.4 and 51.6% in nonneoplastic cases, respectively. Higher VEGF expression was correlated with female sex, left-sided tumors, low tumor-infiltrating lymphocytes, and higher-grade tumors.ConclusionHigher VEGF expression is correlated with RCC development and may be an indicator of poor outcome in RCC patients.