Tumor Vascular Endothelial Growth Factor Expression Research Articles

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosinstaining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-β1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-β1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

VEGF, EGFR and PSMA as possible imaging targets of lymph node metastases of urothelial carcinoma of the bladder

BackgroundIn this study we investigated the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and prostate-specific membrane antigen (PSMA) to analyze their potency as targets for the detection of lymph node (LN) metastases of urothelial carcinoma of the bladder.MethodsAntigen expression was determined in 40 samples with urothelial carcinoma and compared to 17 matched samples without metastases by immunohistochemistry. The total immunostaining score (TIS 0–12) was determined as the product of a proportion score (PS 0–4) and intensity score (IS 0–3).ResultsVEGF expression was high in primary tumor and LN metastases (median TIS 8 in both) and VEGF expression was also seen in LNs without metastases (median TIS 6). EGFR expression was low in primary tumor and LN metastases (median TIS 3 and 2 respectively) and absent in LNs without metastases. PSMA expression was low in samples with urothelial carcinoma (median TIS 2).ConclusionVEGF shows moderate to high expression levels in both primary tumors and LN metastases and could be a candidate as a target agent for imaging modalities of urothelial carcinoma. EGFR and PSMA do show low staining levels in tumor tissue with urothelial carcinoma and do not seem suitable as target agents.Trial registration: The Medical Ethics Review Board of the University Medical Center Groningen approved this study on 14 December 2017 (METc UMCG 2017/639). Trial registration number (UMCG Research Register): 201700868.

Expression of Vascular Endothelial Growth Factor (VEGF) in Colorectal Adenoma and Carcinoma in a Tertiary Care Center.

Colorectal cancer is one of the malignancies in which angiogenesis has been implicated and its importance at different stages of malignant disease. Neovascularization begins when the angiogenic switch is turned on and when angiogenesis activators outweigh angiogenic inhibitors. The process of blood vessel formation is regulated through several growth factor systems. The vascular endothelial growth factor (VEGF) system is one of the important ones and may consequently be a key system in relation to different aspects of colorectal carcinoma treatment.Because of the well-defined steps in its progression (adenoma - Tis - T1 invasive cancer- T2 advanced cancer with metastases), colorectal cancer (CRC) represents a model for investigating the effects of angiogenesis throughout tumor development.The aim of this study is to determine the role of VEGF expression by immunohistochemistry (IHC) in normal epithelium, dysplasia, carcinoma of colorectal specimens and to correlate the same with tumor grade, stage, nodal status, and metastasis. This is a retrospective study on paraffin blocks of 50 colon cancer specimens, 40 adenoma specimens, and 10 normal colonic mucosa specimens. Immunohistochemical stain for VEGF was done on the sections along with controls. Monoclonal antibody detected against VEGF antigen was observed in the cytoplasm of the tumor cells and the intensity ofVEGF expression in individual tumor cells was scored on a scale of 0 (no staining) to 3 (strong intensity), and the percentage of cells with VEGF staining at each intensity was estimated from 0 to 100. Pearson's Chi-squared test and Mann-Whitney test were used to determine significant clinicopathological differences between VEGF expression in positive and negative tumors. In normal epithelium, VEGF immunoreactivity was seen in all 10 cases with high intensity. Among adenomas, VEGF expression was seen in 26 (65%) of the 40 cases. Out of which in tubular adenomas VEGF expression was seen in 13 cases (60%) and negative in eight cases (40%). In tubulo villous adenoma, VEGF expression was seen in nine cases (60%) and negative in six cases (40%). Villous adenomas showed VEGF expression in all four cases (100%). In adenocarcinoma, VEGF expression was seen to be expressed in 42 cases (84%) and negative in eight cases (16%) and expression washigher in low-grade carcinomas (70%) compared to high-grade carcinomas. A significant difference in the expression ofVEGF among adenomas and carcinomas was observedwith higher intensity present in adenoma when compared to carcinoma. Expression ofVEGF could be considered as an early carcinogenic factor incolorectal carcinomas as it is expressed in higher intensity in the precancerous lesion and low-grade and stage 1 adenocarcinoma. Hence, we infer that early colorectal carcinomas are an important model for targeted therapy with antiangiogenic factors for VEGF.

Expression of VHL, VEGF and HIF-1α in endolymphatic sac tumors

Objective: To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation. Methods: Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed. Results: The expression rate of VHL in the ELST group was significantly lower than that in the control group (P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group (P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage (P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST (P>0.05). Conclusions: The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.

Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.

The Association between Vascular Endothelial Growth Factor (VEGF) Expression and Various Pathological Parameters of Squamous Cell Carcinoma of Uterine Cervix in Sanglah General Hospital

Cervical cancer is the second most common malignancy in women with increasing morbidity and mortality rate. VEGF is known as one of pro-angiogenic factors that induce angiogenesis in various malignancy. VEGF overexpression is associated with poor prognosis and plays an important role in cervical cancer progression. This study aimed to investigate the association between VEGF expression and pathological parameters of squamous cell carcinoma of uterine cervix in Sanglah General Hospital Denpasar. This is a cross-sectional study design. The sampel size was 36 paraffin blocks which were selected by consecutive sampling. Pathological parameter data were divided into 2 categories; tumor size (£4 cm, &gt;4 cm), tumor extension (intra and extra-uterine), lymphatic vascular invasion (positive, negative), vascular density (low, high) and lymph node metastasis (positive, negative). VEGF expressions were examined by imunohistochemical technique and evaluated by Histo-Score method. All variables were analyzed by Chi-square analysis with significance value p &lt;0.05. Chi-square analysis revealed an association between tumor size and VEGF expression (p=0.035). In addition, large tumor size (&gt;4 cm) has 2.17 times probability of causing high VEGF expression. VEGF expression were not associated with tumor extension (p=0.502), lymphatic vascular invasion (p=0.346), vascular density (p=0.364) and lymph node metastasis (p=0.209). This study has proved that tumor size is associated with VEGF expression. Large tumor size has greater risk of causing high VEGF expression therefore anti-VEGF targeted therapy could be proposed in large tumor size. There were no association between VEGF expression and tumor extension, lymphatic vascular invasion, vascular density and lymph node metastasis.&#x0D; &#x0D; Keywords: VEGF expression, squamous cell carcinoma, uterine cervix.

Clinical and prognostic features of MMP-2 and VEGF in AEG patients.

Adenocarcinoma of the esophagogastric junction (AEG) has been increased in recent years and has become a worldwide problem that seriously affects human health. The purpose of the study is to investigate the clinical and prognostic characteristics of the matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression in AEG patients. A total of 69 patients were enrolled in this study. The result showed that the high expression of MMP-2 was significantly associated with tumor differentiation (P < 0.05) and depth of invasion (pT, P < 0.05). The high expression of VEGF was significantly associated with pT (P < 0.05) and lymph node metastasis (pN, P < 0.05). There was a positive correlation between MMP-2 and VEGF expression (P < 0.01). The 5-year survival rate for the 69 AEG patients was 40.6% and it was significantly associated with tumor differentiation (P < 0.05), pN (P < 0.01), pTNM stage (P < 0.01), MMP-2 expression (P < 0.05), and VEGF expression (P < 0.05). Cox multivariate regression demonstrated that tumor differentiation and pN were independent factors for the 5-year survival rate. Our study showed that MMP-2 and VEGF could work synergistically in AEG development.

Ultrasound-Targeted Microbubble Destruction Enhances Inhibitory Effect of Apatinib on Angiogenesis in Triple Negative Breast Carcinoma Xenografts.

Ultrasound-targeted microbubble destruction (UTMD) has been proven as an effective technique to assist drugs to cross the vascular wall and cell membrane. This study was aimed at evaluating the synergistic antiangiogenic and growth-inhibiting effects of apatinib (APA) and UTMD on the triple negative breast cancer (TNBC). The TNBC xenograft model was established in nude mice (n = 40) which were then randomly divided into the APA plus UTMD (APA-U) group, UTMD group, APA group, and model control (M) group (n = 10 per group). Corresponding treatment was done once daily for 14 consecutive days. The general condition and body weight of tumor-bearing nude mice were monitored. Routine blood test and detection of liver and kidney function were done after treatments. The tumor size and microcirculation were examined by two-dimensional ultrasonography (2DUS) and contrast-enhanced ultrasonography (CEUS), respectively. Then, the tumor tissues were harvested for the detection of vascular endothelial growth factor (VEGF) by immunohistochemistry and for CD31-PAS double staining to assess microvessel density (MVD) and heterogeneous vascular positivity rate. After treatments, the tumor growth and angiogenesis were significantly inhibited in the APA group and the APA-U group, and these effects were more obvious in the APA-U group. The tumor volume, CEUS parameters, VEGF expression, and MVD in the APA-U group were significantly lower than those in the APA group (P < 0.05), while there were no marked differences in the heterogeneous vascular positivity rate, body weight, and blood parameters between the two groups (P > 0.05). In the UTMD group, the tumor growth and angiogenesis were not significantly inhibited, and all the parameters were similar to those in the M group (P > 0.05). During the experiment, all mice survived and generally had good condition. In conclusion, APA combined with UTMD may exert synergistic antiangiogenic and growth-inhibiting effects on the TNBC and not increase the heterogeneous vasculature and the severity of APA-related systemic side effects.

Perifocal edema volume is not associated with immunohistochemical features reflecting proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis

ObjectivePerifocal edema of brain tumors is associated with survival and neurological symptoms. Our aim was to analyze associations between perifocal edema and immunohistochemical features including proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis (BM). Methods35 patients with BM were included into the retrospective study. The tumors were localized supratentorial in 25 lesions (71.4%) and infratentorial in 10 lesions (28.6%). The following immunohistochemical features were calculated on histopathological specimens: microvessel density, proliferation index Ki 67, matrix-metallopeptidase 9 (MMP9) extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) expression. Tumor and edema volumes were estimated semiautomatically on magnetic resonance images. ResultsThere were no correlations between tumor volume and edema volume. Moreover, no correlation was identified between the investigated immunohistochemical features and tumor/edema volume. In the non-small cell lung cancer subgroup, a positive correlation between tumor volume and VEGF expression was observed (r = 0.52, P = 0.02) and edema volume correlated inversely with MMP9 expression (r = −0.53, P = 0.02). ConclusionIn BM, no linear associations exist between tumor volumes, edema volumes and immunohistochemical features reflecting proliferation potential, neoangiogenesis, microvessel density and MMP9 expression. However, in the subgroup of non-small cell lung cancer, there might be associations between MMP9 expression and edema volume as well as between tumor volume and angiogenesis.

Associations Between FDG PET and Expression of VEGF and Microvessel Density in Different Solid Tumors: A Meta-analysis

To date, there are inconsistent data about relationships between 2-deoxy-2 [18F] fluoro-D-glucose positron emission tomography (FDG-PET) and expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD). The aim of the present meta-analysis was to systematize the reported data about associations between maximal standardized uptake value (SUVmax) derived from FDG PET and expression of VEGF and as well as MVD. MEDLINE library, SCOPUS and EMBASE data bases were screened for relationships between SUVmax and VEGF/MVD up to October 2019. Overall, in 18 studies correlations between SUVmax and VEGF and in 13 studies correlations between SUVmax and MVD were reported. The following data were extracted from the literature: authors, year of publication, number of patients, and correlation coefficients. Associations between 18F-FDG PET and VEGF were reported in 18 studies (935 patients). The calculated correlation coefficients between SUVmax and VEGF expression ranged from -0.16 to 0.88. The pooled correlation coefficient was 0.32, (95% confidence interval [CI] = [0.15; 0.48]). Associations between 18F-FDG PET and MVD were investigated in 13 studies (593 patients). The reported correlation coefficients ranged from -0.23 to 0.91. The pooled correlation coefficient was 0.27, (95% CI = [0.00; 0.53]). Analysis of MVD based on CD105 immunohistochemical staining was performed in four studies (117 patients). The pooled correlation coefficient was 0.41 (95% CI = [0.22; 0.59]). In three reports with 233 patients, MVD was estimated by staining with CD31 antibody. The pooled correlation coefficient was 0.01, (95% CI = [-0.44; 0.47]). Finally, in 9 studies (280 patients) MVD was performed on CD34 stained specimens. The pooled correlation coefficient was 0.36, (95% CI = [0.09; 0.63]). SUVmax of FDG PET correlated weakly with expression of VEGF and with MVD. Therefore, FDG PET cannot predict neoangiogenesis in malignant tumors.

Evaluation of VEGF expression correlates with COX-2 expression in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma

Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (AdCC) are the most common benign and malignant salivary gland tumors. Cyclooxygenase-2 (COX-2) is a key regulatory enzyme that its overexpression in various tumors is correlated with progression, metastasis, and apoptosis inhibition. Vascular endothelial growth factor (VEGF) is a potent angiogenic mediator that has an important role in neoplastic angiogenesis. The aim of this study was to immunohistochemically analyze the expression of COX-2 and VEGF and to compare the expression of benign and two malignant salivary gland tumors with varied structures. In this cross-sectional study, 90 specimens including 30 cases of each tumor were retrieved. Immunohistochemical staining of COX-2 and VEGF was performed for all the samples. The percentage of positive tumor cells and staining intensity was evaluated by two pathologists blindly. Data were analyzed by Chi-square and Gamma test and P < 0.05. A statistically significant difference was noted between the expression and intensity of COX-2 and VEGF in PA, MEC, and AdCC (P < 0.05). A significant correlation was observed between COX-2 and VEGF expression in MEC and AdCC (P < 0.05). However, no significant correlation was found between the expression and intensity of COX-2 and VEGF with histologic grade and lymph node metastasis in MEC and AdCC (P < 0.05). High expression of VEGF and COX-2 in malignant tumors compared to PA suggested the role of both markers in malignant transformation. The significant correlation of VEGF expression with COX-2 may represent the role of COX-2 in tumor angiogenesis by modulating VEGF production.

Association Between VEGF Expression and Diffusion Weighted Imaging in Several Tumors-A Systematic Review and Meta-Analysis.

To date, only a few studies have investigated relationships between Diffusion-weighted imaging (DWI) and Vascular endothelial growth factor (VEGF) expression in tumors. The reported results are contradictory. The aim of the present analysis was to review the published results and to perform a meta-analysis regarding associations between apparent diffusion coefficients (ADC) derived from DWI and VEGF expression. MEDLINE library was screened for relationships between ADC and VEGF expression up to January 2019. Overall, 14 studies with 578 patients were identified. In 10 studies (71.4%) 3 T scanners were used and in four studies (28.6%) 1.5 T scanners. Furthermore, seven studies (50%) had a prospective design and seven studies (50%) had a retrospective design. Most frequently, prostate cancer, followed by rectal cancer, cervical cancer and esophageal cancer were identified. The pooled correlation coefficient of all tumors was r = −0.02 [95% CI −0.26–0.21]. ADC values derived from routinely acquired DWI do not correlate with VEGF expression in various tumors. Therefore, DWI is not sensitive enough to reflect angiogenesis-related microstructure of tumors.

OVEREXPRESSION VASCULAR ENDOTHELIAL GROWTH FACTOR IN NASOPHARYNGEAL CARCINOMA WITH UNDIFFERENTIATED CARCINOMA TYPE IN ADVANCED STAGE

Introduction:&#x0D; Nasopharyngeal Carcinoma (NPC) is a malignancy that tends to diagnosed at an advanced stage with low survival and prognosis rate. One of the factors that may play a role in progressivity and metastasis of tumor is overexpression of vascular endothelial growth factor (VEGF), which is a key role in tumor angiogenesis.&#x0D; Objective:&#x0D; This study aims to learn the expression of VEGF in NPC with Undifferentiated Carcinoma type and to learn the association pf VEGF Expression with tumor stage of NPC&#x0D; Method:&#x0D; This is a cross-sectional study performed in ENT-HNS Department of ENT-HNS of Udayana University/Sanglah Hospital. The sample was collected by consecutive nonprobability sampling, starting from January 2016. NPC patients underwent Histopathologic examination from a nasopharyngeal biopsy. The result is Undifferentiated Carcinoma. VEGF expression analyzed by red-brown stained cytoplasm. Data were analyzed by Spearman's Correlation Test Chi-Square test, and Paired Sample t-Test.&#x0D; Result:&#x0D; VEGF positive Expression was found in 27 of 28 (96.4%) Undifferentiated Carcinoma type of NPC cases. VEGF overexpression was found in 23 of 28 (82.4%) Undifferentiated Carcinoma type of NPC cases.There is significant correlation found between tumor stage and VEGF expression (p&lt;0.05).&#x0D; Conclusion: &#x0D; From the research, it could conclude that there is significant correlation between tumor stage and VEGF Expression.

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

Photodynamic therapy (PDT) is a treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels and microvessel density (MVD) in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations and microvessel density in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT.

The Potential Roles of MELF-Pattern, Microvessel Density, and VEGF Expression in Survival of Patients with Endometrioid Endometrial Carcinoma: A Morphometrical and Immunohistochemical Analysis of 100 Cases.

BackgroundIn this study, we hypothesized that microcystic, elongated, fragmented (MELF)-pattern, vascular endothelial growth factor (VEGF) expression by cancer cells and microvessel density of cancer stroma may be associated with progression of endometrioid adenocarcinoma.MethodsThe study used data from the Belarus Cancer Registry and archival histological material of 100 patients with retrospectively known good (survival) and poor (disease progression and death) outcomes. All cases were immunohistochemically stained for CD34 and VEGF. Two independent samples were compared for the characteristics of signs, and obtained results were analyzed by receiver operating characteristic analysis, Mann-Whitney U test, χ2 test (Yates correction), and Mantel-Cox test. Multivariate Cox hazard analysis and Spearman correlation test were used. A p-value of less than .05 was considered statistically significant.ResultsThe observed survival rate of patients with endometrioid adenocarcinoma was significantly lower (p = .002) in MELF-pattern positive patients when compared with MELF-pattern negative patients. The overall survival rate of patients whose tumors had more than 114 vessels/mm2 of tissue was significantly low (p < .001). Interestingly, a similar observation was found in patients with increased vessel area, evidenced by VEGF expression in the glandular tumor component.ConclusionsOur study suggests, for the first time, that these criteria may be used as risk factors of endometrioid adenocarcinoma progression during 5 years after radical surgical treatment. However, a large independent cohort of samples should be considered in the future to validate our findings.

The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis.

Vascular endothelial growth factor (VEGF) serum level or tumor expression may be prognostic in renal cell carcinoma (RCC). The purpose of this meta-analysis was to examine the prognostic value of serum VEGF level and tumor expression in patients with RCC. PubMed and EMBASE databases were searched until September 26, 2016. Prospective and retrospective studies of RCC patients that had VEGF levels measured were included. Outcome measures were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). A total of 14 studies were included in the meta-analysis. In patients with RCC, elevated serum VEGF level was not associated with OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60; p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to 8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001). Removal of one study, however, resulted in elevated serum level being associated with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR = 1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). In patients with RCC, elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor expression is only associated with worse DSS. The number of studies, however, was limited and the results should be interpreted with caution.

Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma.

Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth.

Immunohistochemical expression of vascular endothelial growth factor in keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst: A comparative study.

Background:Cyst and tumors arise from tissue remains of odontogenesis, these interactions have been considered to play an important role in the tumorigenesis of odontogenic lesions. The connective tissue stroma has an essential role in the preservation of epithelial tissues and minor alterations in the epithelium are followed by corresponding changes in the stroma, such as angiogenesis. Vascular endothelial growth factor (VEGF) is considered the first factor which maintains its position as the most critical driver of vascular formation and is required to initiate the formation of immature vessels, with this aim, present study was executed to evaluate VEGF expression in kertocystic odontogenic tumor, dentigerous cyst and radicular cyst (RC).Materials and Methods:A retrospective study was carried out comprising a total of 31 cases; 13 cases of keratocystic odontogenic tumor (KCOT), nine cases of dentigerous cyst (DC) and nine cases of RC. The sections were stained immunohistochemically with VEGF antibody and were evaluated for the presence and intensity of the immuno reactive cells. Statistical analysis was carried out using Chi-square test to inter-compare the VEGF expression between KCOT, DC, and RC.Results:VEGF expression in the epithelium and connective tissue was significantly higher in KCOT compared to dentigerous and RC. One case of KCOT with carcinomatous change also revealed positive results for the VEGF expression in the dysplastic epithelium, tumor islands, and connective tissue. The significant difference was observed on inter-comparison of the VEGF expression in the connective tissue of KCOT and DC, whereas no significant difference was observed in the VEGF expression in the connective tissue of KCOT and DC.Conclusion:The present study data supports the literature finding that angiogenesis can be important in the progression and enlargement of odontogenic cysts similarly to what occurs in neoplastic conditions and further it can be concluded that the higher positivity for VEGF of KCOT could help to explain in part the aggressive biological behavior of the lesion. The stroma of KCOT could be regarded not only as a structural support of the cyst wall but also as playing a part in the neoplastic behavior of cyst.