Association of sirtuin-1 and vascular endothelial growth factor expression with tumor progression and poor prognosis in liposarcoma

Objectives A relationship exists between sirtuin-1 expression and growth and survival of malignant tumors. This study aimed to investigate the prognostic value of sirtuin-1 and vascular endothelial growth factor (VEGF) expression in patients with liposarcoma by examining associations between their expression levels and clinical outcomes. Methods Clinical and histopathological characteristics and follow-up and survival information were retrospectively reviewed for 42 liposarcoma cases. Sirtuin-1 and VEGF protein expression levels were evaluated by immunohistochemistry and their associations with clinical parameters were analyzed using the Spearman-rho test. Univariate and multivariate Cox regression analyses were performed to identify potential prognostic factors. Kaplan–Meier analysis was performed to analyze overall survival. Results Sirtuin-1 and VEGF protein expression levels were significantly associated with histological grade, metastasis, and American Joint Committee on Cancer stage. A significant positive correlation was observed between sirtuin-1 and VEGF expression levels (R = 0.677). In univariate analysis, sirtuin-1 and VEGF expression were correlated with shorter overall survival, but the association was significant only for sirtuin-1 (hazard ratio = 3.752, 95% confidence interval 1.553–9.062) in multivariate analysis. Conclusion Sirtuin-1 and VEGF expression levels are significantly correlated with progression of liposarcoma, and sirtuin-1 expression significantly predicts a poor prognosis in patients with liposarcoma.

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The role of vascular endothelial growth factor as a prognostic and clinicopathological marker in osteosarcoma: a systematic review and meta-analysis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02888-3 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Chao Zhang ◽

Lin Wang ◽

Chuang Xiong ◽

Runhan Zhao ◽

Hao Liang ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Overall Survival ◽

Growth Factor ◽

Meta Analysis ◽

Disease Free Survival ◽

Vascular Endothelial ◽

Vegf Expression ◽

Free Survival ◽

Endothelial Growth Factor ◽

Disease Free

Abstract Background In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma. Methods We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma. Results A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87–3.11, p < 0.001) and disease-free survival (HR, 2.604; 95% CI, 1.698–3.995, p < 0.001), respectively. Furthermore, investigation regarding osteosarcoma clinicopathologic characteristics suggested that high VEGF expression was significantly associated with metastasis (OR, 4.39; 95% CI, 2.77–6.95; p < 0.001), clinical stage (OR, 0.73; 95% CI, 0.62–0.87; p < 0.001), and microvessel density (SMD, 3.33, 95% CI,1.57–5.10, p < 0.001), but not associated with tumor location, gender, age, local recurrence, and chemotherapy response. Conclusion Our meta-analysis findings suggest that elevated VEGF expression may be a predictive biomarker for poor prognosis and adverse clinicopathological characteristics in patients with osteosarcoma.

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Correlation of Vascular Endothelial Growth Factor Expression to Overall Survival in Feline Invasive Mammary Carcinomas

Veterinary Pathology ◽

10.1354/vp.39-6-690 ◽

2002 ◽

Vol 39 (6) ◽

pp. 690-696 ◽

Cited By ~ 44

Author(s):

F. Millanta ◽

G. Lazzeri ◽

I. Vannozzi ◽

P. Viacava ◽

A. Poli

Keyword(s):

Vascular Endothelial Growth Factor ◽

Overall Survival ◽

Growth Factor ◽

Mammary Tumors ◽

Vascular Endothelial ◽

Vegf Expression ◽

Mammary Carcinomas ◽

Endothelial Growth Factor ◽

Microvessel Counts

Samples from feline invasive mammary carcinomas (FMCs) were used to determine the prognostic significance of the immunohistochemical expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD). Forty-eight queens bearing FMCs were included in a 2-year follow-up study. Mammary tumors were classified according to the World Health Organization system and graded on the basis of histologic criteria. Tumor sections were immunostained using anti-VEGF and anti-von Willebrand factor (vWf) antibodies. VEGF expression was quantified on the basis of the percentage of positive cells. MVD of vWf-positive microvessels was determined by both mean microvessel counts and highest microvessel counts. Normal mammary gland tissues showed an inconspicuous VEGF staining. In FMCs the proportion of VEGF-positive cells was significantly higher in papillary and solid carcinomas than in tubular and papillary cystic tumors. An increased number of cells expressing VEGF was also observed in poorly differentiated FMCS. Sixteen (33.3%) of the queens bearing invasive carcinomas were still alive at the end of the 2-year follow-up period, and 32 (66.7%) had died. The VEGF expression was significantly correlated with the clinical outcome, but no correlation was observed with the invasion of lymphatic vessels. A correlation between the higher percentage of VEGF-positive cells and the unfavorable prognosis was demonstrated by the estimation of curves for overall survival ( P = 0.03). Univariate analysis showed that MVD did not correlate with the overall survival. The results of our study demonstrated that VEGF expression, although not associated with increased angiogenesis, is a prognostic indicator in feline mammary tumors. In contrast, there is no support for a role of neovascularization as an indicator of survivability.

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Clinical significance of vascular endothelial growth factor expression in patients with carcinoma of the mouth floor and tongue

Vojnosanitetski pregled ◽

10.2298/vsp0906440b ◽

2009 ◽

Vol 66 (6) ◽

pp. 440-448 ◽

Cited By ~ 5

Author(s):

Miroslav Brocic ◽

Ruzica Kozomara ◽

Snezana Cerovic ◽

Nebojsa Jovic ◽

Slobodanka Vukelic-Markovic ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Overall Survival ◽

Growth Factor ◽

Clinical Significance ◽

Nuclear Grade ◽

Stage Ii ◽

Vascular Endothelial ◽

Vegf Expression ◽

Oral Cancers ◽

Endothelial Growth Factor

Background/Aim. Although there are several types of malignant oral cancers, more than 90% of all diagnosed oral cancers are squamous cell carcinoma (OSCC). Angiogenesis is a cascade-like mechanism which is essential for tumor growth and metastasis. Therefore, vascular endothelial growth factor (VEGF) expression in OSCC and its effect on clinicopathological characteristics and prognosis is of major interest. So far researches have shown that increased expression of this gene, in other words enhanced synthesis of this protein (VEGF), independently on other factors, increases a chance for local relapse, and distant metastasis. Consequently, patients with OSCC have poor disease-free survival, as well as poor overall survival. The aim of the study was to determine clinical significance of VEGF expression in patients with stage II and III OSCC. Methods. This retrospective study analyzed 40 patients who had been operated for OSCC of their tongue and the mouth floor. Of these patients, some had stage II and III OSCC with histological grade, G1-G3 and nuclear grade Ng1-Ng3. Two high quality tissue samples were obtained and immunohistochemical expression of VEGF was quantitatively determined by using high microscope amplification. The value of VEGF expression of 20% was rated as significant expression, whereas tumor cells reactivation less than 20% was considered very low or no expression at all. The patients were followed up for a 3-year period. Results. The obtained results showed that 11 (17.5%) patients had VEGF expression less than 20% and 29 (82.5%) above 20%. A statistical significance was immanent with positive nodal status (p < 0.05) and disease stage (p < 0.05). No statistical correlation was found between the level of VEGF expression and histological and nuclear grade, tumor size, disease relapse or patients overall survival. Conclusion. In spite the controversy about the prognostic relevance of VEGF our results as well as the results of previous studies, suggest that the expression of VEGF is not reliable as a clinical parameter for the prognosis and disease outcome but it is one of the important factors for the disease progression.

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Regulation of Vascular Endothelial Growth Factor Gene Expression in Murine Macrophages by Nitric Oxide and Hypoxia

Experimental Biology and Medicine ◽

10.1177/153537020322800608 ◽

2003 ◽

Vol 228 (6) ◽

pp. 697-705 ◽

Cited By ~ 38

Author(s):

Madhuri Ramanathan ◽

Avi Giladi ◽

S. Joseph Leibovich

Keyword(s):

Nitric Oxide ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Cell Density ◽

Vascular Endothelial ◽

Vegf Expression ◽

Ifn Γ ◽

Cell Densities ◽

Endothelial Growth Factor ◽

Vegf Protein

Vascular endothelial growth factor (VEGF) expression in murine peritoneal macrophages is strongly upregulated by hypoxia via transcriptional and posttranscriptional mechanisms. Interferon-γ (IFN-γ) with Escherichia coll lipopolysaccharide (LPS) also upregulates expression of VEGF, as well as of the inducible nitric oxide synthase (INOS). Hypoxia (1% O2) upregulates VEGF expression in macrophages from both wild-type and INOS knockout mice, indicating that hypoxic upregulation of VEGF is independent of INOS. However, the INOS inhibitor aminoguanidine (AG) decreases the VEGF expression induced by LPS/IFN-γ, indicating an important role for NO. NO-dependent induction of VEGF is strongly dependent on cell density. LPS/IFN-γ treatment induces minimal VEGF protein expression in macrophages cultured at low cell densities (<0.25 × 106 cells/cm2); at higher cell densities (>0.25 × 106 cells/cm2) that lead to conditions of pericellular hypoxia, however, induction of VEGF expression was strong. Transient transfection of RAW 264.7 cells with luciferase reporter constructs of the murine VEGF promoter indicates that both hypoxia and LPS/IFN-γ independently induce VEGF promoter activity, irrespective of cell density. Although LPS/IFN-γ treatment induces transcriptional activation of the VEGF promoter, significant levels of VEGF protein are only expressed by cells at high density under conditions of pericellular hypoxia. This suggests an important regulatory role for hypoxia at the posttranscriptional level. Deletion analysis of the VEGF promoter shows that the hypoxia response element region and its immediate flanking sequences are essential for both hypoxia and LPS/IFN-γ-induced VEGF promoter activation.

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Vascular endothelial growth factor-C (VEGF-C) overexpression is correlated with poor prognosis in intrahepatic cholangiocarcinoma (CCC)

Gastroenterology ◽

10.1016/s0016-5085(01)81291-9 ◽

2001 ◽

Vol 120 (5) ◽

pp. A261-A261 ◽

Cited By ~ 1

Author(s):

Y PAIK ◽

Y KIM ◽

S PARK ◽

J CHUNG ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Vascular Endothelial ◽

Factor C ◽

Endothelial Growth Factor

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Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02843-x ◽

2021 ◽

Author(s):

Takao Kamai ◽

Toshiki Kijima ◽

Toyonori Tsuzuki ◽

Akinori Nukui ◽

Hideyuki Abe ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Vascular Endothelial Growth Factor ◽

Overall Survival ◽

Cell Death ◽

Growth Factor ◽

Vascular Endothelial ◽

Primary Tumors ◽

Anti Vegf ◽

Programmed Cell Death 1 ◽

Endothelial Growth Factor

Abstract Background Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both. Methods In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody. Results Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival. Conclusions Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.

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