Vascular Endothelial Growth Factor (VEGF-C) Protein Expression Related with Lymphangiogensis in Iraqi Cervical Cancer Patients

2019 ◽  
pp. 27-40
Keyword(s):  
Cervical Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
P Value ◽  
Vascular Endothelial ◽  
Chi Square ◽  
C Protein ◽  
Cervical Cancer Cells ◽  
Endothelial Growth Factor

Objective: Metastatic spread of tumor cells to distant organs is the leading cause of mortality from cancer. Although metastatic tumor spread can occur via a different mechanism. lymphangiogenic factors recognized were vascular endothelial growth factor (VEGF)–C and –D, which bind to a tyrosine kinase receptor, VEGF receptor (R)–3. Binding affinities to VEGFR-2 receptor increase on the lymphatic and blood endothelium therefore enables both growth factors to also exert lymphangiogenic and angiogenic effects and increased incidence of lymph node metastasis. The aim of this study is to evaluate the VEGF-C protein expression in cervical cancer cells and lymph vessels and found the relationship of this marker with lymphangiogensis of Iraqi cervical cancer samples. Method: In this study, expression of VEGF-C was noticed in 55 cervical samples by Immuno- histochemistry. 35 cases diagnosed as invasive cervical cancer in addition to 20 normal samples consider as control. Immunohistochemistry was performed and the cytoplasm level of VEGF-C was scored by the percentage of positive cells and intensity. Results: The present data evaluated the prognostic significance of VEGF-C to cervical cancer, cytoplasm staining was seen in 29 cases (82.9 %) in cervical cancer tissues. Only 4 out of 35 cases (11.4 %) displayed cytoplasmic and nuclear tissue. There is significant difference of VEGF-C staining in lymphatic vessels and cancer cells (χ2= 5.04, p = 0.023*) regarding to positive expression (20/ 57.1%), (25/ 71.4 %) respectively and negative VEGF-C staining 15 (42.9%), 10 (28.6 %) respectively. High positive percentage of VEGF-C expression in cytoplasm of malignant cases in score 2& 3 (25.7%, 45.7 %, P-value= 0.0392 *, 0.029* respectively) as compared to normal cases (15%, 30% respectively). Demographic criteria of patients revealed association with VEGF-C expression patterns. Differentiation Well + moderately and histologic type Squamous carcinoma showed significantly associated with VEGF-C (P=0.0071** & 0.0071** respectively). Positive VEGF-C staining in cancer cells had more lymphatic vessel (17/68 %) as compared to negative cases (3/30 %) with Chi-Square 8.263, p value= 0.0061**. Also, positive VEGF-C staining had more lymph node associated (9/36%) compared to negative cases (1/10 %) with Chi-Square 13.503, p value= 0.0001**. Conclusion: In conclusion, high expression of vascular endothelial growth factor was noticed in cervical cancer cells and lymph vascular invasion indicating the important role of this marker as prognostic factor for Iraqi cervical cancer. Additionally, these results suggested that VEGF-C promoted cervical cancer metastasis using immunohistochemistry technique. Our findings offer new vision into the role of VEGF-C in cervical cancer development and give potential target for study the lymphangiogensis of tumor in Iraqi women.

A novel approach for the discrimination of culture medium from Vascular Endothelial Growth Factor (VEGF) overexpressing colorectal cancer cells

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sinem Tunçer ◽  
Rafig Gurbanov
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Ftir Spectroscopy ◽  
Cancer Cells ◽  
Lower Amount ◽  
Vascular Endothelial ◽  
Colorectal Cancer Cells ◽  
Endothelial Growth Factor

AbstractObjectivesThe expression level of Vascular Endothelial Growth Factor (VEGF) is assumed as a prognostic marker for several tumor types, including colorectal cancer. Therefore, the determination of pre- and post-therapy levels of VEGF appears to have great value in the assessment of tumor prognosis. Enzyme-Linked Immunosorbent Assay (ELISA) is commonly used for the determination of serum or plasma VEGF levels, but the method is costly and time-consuming. In this study, we aimed to describe a rapid and cost-effective analysis method to discriminate VEGF overexpressing colorectal cancer-derived conditioned medium (CM).MethodsAttenuated Total Reflection (ATR)-Fourier Transform Infrared (FTIR) spectroscopy, combined with Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), was used to differentiate VEGF overexpressing colorectal cancer cell line CM from CM obtained from the corresponding control cells which express and secrete relatively lower amount of VEGF.ResultsSamples belong to VEGF overexpressing colorectal cancer cells were clearly distinguished from the control group with very high PC scores as PC1 + PC2 = 96%. Besides, a 100% accurate distinction between these two groups was achieved by the LDA analysis.ConclusionsATR-FTIR spectroscopy combined with pattern recognition techniques was able to discriminate CM of VEGF overexpressing colorectal cancer cells with high efficiency and accuracy.

scholarly journals HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression

2001 ◽  
Vol 21 (12) ◽  
pp. 3995-4004 ◽  
Author(s):  
Erik Laughner ◽  
Panthea Taghavi ◽  
Kelly Chiles ◽  
Patrick C. Mahon ◽  
Gregg L. Semenza
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Half Life ◽  
Hypoxia Inducible Factor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Her2 Signaling ◽  
Endothelial Growth Factor

ABSTRACT Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator composed of HIF-1α and HIF-1β subunits. Several dozen HIF-1 targets are known, including the gene encoding vascular endothelial growth factor (VEGF). Under hypoxic conditions, HIF-1α expression increases as a result of decreased ubiquitination and degradation. The tumor suppressors VHL (von Hippel-Lindau protein) and p53 target HIF-1α for ubiquitination such that their inactivation in tumor cells increases the half-life of HIF-1α. Increased phosphatidylinositol 3-kinase (PI3K) and AKT or decreased PTEN activity in prostate cancer cells also increases HIF-1α expression by an undefined mechanism. In breast cancer, increased activity of the HER2 (also known as neu) receptor tyrosine kinase is associated with increased tumor grade, chemotherapy resistance, and decreased patient survival. HER2 has also been implicated as an inducer of VEGF expression. Here we demonstrate that HER2 signaling induced by overexpression in mouse 3T3 cells or heregulin stimulation of human MCF-7 breast cancer cells results in increased HIF-1α protein and VEGF mRNA expression that is dependent upon activity of PI3K, AKT (also known as protein kinase B), and the downstream kinase FRAP (FKBP-rapamycin-associated protein). In contrast to other inducers of HIF-1 expression, heregulin stimulation does not affect the half-life of HIF-1α but instead stimulates HIF-1α synthesis in a rapamycin-dependent manner. The 5′-untranslated region of HIF-1α mRNA directs heregulin-inducible expression of a heterologous protein. These data provide a molecular basis for VEGF induction and tumor angiogenesis by heregulin-HER2 signaling and establish a novel mechanism for the regulation of HIF-1α expression.

scholarly journals Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481878935 ◽  
Author(s):  
Monika Zajkowska ◽  
Monika Zbucka-Krętowska ◽  
Iwona Sidorkiewicz ◽  
Emilia Lubowicka ◽  
Grażyna Ewa Będkowska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Plasma Levels ◽  
Statistical Significance ◽  
Ca 125 ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Metalloproteinase 9

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.

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