Decrease In Serum Vascular Endothelial Growth Factor Levels Research Articles

Poems

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating polyneuropathy with plasma cell dyscrasia, overproduction of vascular endothelial growth factor (VEGF), and multiorgan involvement. VEGF is likely to play an important role in the pathogenesis of the disorder by its strong action on neo-vasculization and increased vascular permeability. POEMS syndrome is serious disease, because of progressive neuropathy and massive pleural effusion/ascites. There is no established treatment guideline. However, in appropriate candidates, high-dose chemotherapies with autologous peripheral blood stem cell transplantation results in obvious clinical improvement with a significant decrease in serum VEGF levels. For patients who are not indicated for transplantation, a recent randomized trials has shown efficacy of thalidomide. Treatments that should be considered as future therapy include lenalidomide and bortezomib or other proteasome inhibitors. The efficacy of anti-VEGF monoclonal antibody (bevacizumab).is controversial. By induction of these novel treatments after 2000, the prognosis of POEMS syndrome has been significantly improved.

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial.

Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome (PCOS) and may contribute to increased risk of ovarian hyperstimulation syndrome (OHSS) in affected individuals. Vitamin D (VitD) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions. Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our understanding of the pathophysiology of this syndrome. It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels. Therefore, we aimed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS. This is a randomized placebo-controlled trial conducted between October 2013 and March 2015. Sixty-eight VitD-deficient women with PCOS were recruited. Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks. There was a significant decrease in serum VEGF levels (1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL–1; p < 0.001) in the VitD group. Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals, Ferriman-Gallwey hirsutism score, and triglycerides following VitD supplementation. Interestingly, ∆VEGF was positively correlated with ∆triglycerides (R2 = 0.22; p = 0.02) following VitD supplementation. In conclusion, VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS. This is a novel molecular explanation for the beneficial effects of VitD treatment. It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS.

Role of Microvessel Density and Vascular Endothelial Growth Factor in Angiogenesis of Hematological Malignancies.

Angiogenesis plays an important role in progression of tumor with vascular endothelial growth factor (VEGF) being key proangiogenic factor. It was intended to study angiogenesis in different hematological malignancies by quantifying expression of VEGF and MVD in bone marrow biopsy along with serum VEGF levels and observing its change following therapy. The study included 50 cases of hematological malignancies which were followed for one month after initial therapy along with 30 controls. All of them were subjected to immunostaining by anti-VEGF and factor VIII antibodies on bone marrow biopsy along with the measurement of serum VEGF levels. Significantly higher pretreatment VEGF scores, serum VEGF levels, and MVD were observed in cases as compared to controls (p < 0.05). The highest VEGF score and serum VEGF were observed in chronic myeloid leukemia and maximum MVD in Non-Hodgkin's Lymphoma. Significant decrease in serum VEGF levels after treatment was observed in all hematological malignancies except for AML. To conclude angiogenesis plays an important role in pathogenesis of all the hematological malignancies as reflected by increased VEGF expression and MVD in bone marrow biopsy along with increased serum VEGF level. The decrease in serum VEGF level after therapy further supports this view and also lays the importance of anti angiogenic therapy.

Plasma VEGF levels may not accurately reflect the truth all the time

To the editor, We read with great interest the study by She-Juan An et al., which showed that posttreatment plasma VEGF levels associated with the overall survival of patients with advanced non-small-cell lung cancer treated with bevacizumab plus chemotherapy. In this study, before and 6 weeks after treatment, vascular endothelial growth factor (VEGF) levels measured. Also, this study showed that low posttreatment VEGF levels associated with better overall survival (OS) [1]. We have some insights for this decrease in serum VEGF levels. VEGF circulating in the blood of patients with cancer may be derived from various sources, as depicted in Fig. 1. Circulating levels of VEGF are dependent on the amount released from tumor cells (Fig. 1A) and/or platelets activated at the tumor-vessel endothelium. Activated platelets release VEGF (Fig. 1B), and platelet consumption causes increased levels of thrombopoietin, which in turn stimulates megakaryopoiesis and platelet production in the bone marrow. Newly produced platelets are larger in size than those produced during steady-state thrombopoiesis, and therefore contain an elevated amount of VEGF (Fig. 1C). Finally, host immune cells as macrophages that infiltrate tumor tissues can be an additional source of VEGF (Fig. 1 D) [2]. Serum VEGF levels have also been found to correlate with platelet count in a mixed population of metastatic cancers and renal cancer, and some investigators have also stated that VEGF should be corrected for platelet counts. To correct for variation in platelet counts between patients, it has been proposed that the concentration of VEGF per platelet (pg/10) can be calculated by dividing the serum VEGF concentration (pg/ml) by the platelet count (910/ml) [3]. In the study, She-Juan An et al., mean VEGF levels decreased from 81.5 pg/ml to 50.5 pg/ml after 6 weeks of treatment (P = 0.08), with a mean reduction of 31 pg/ml in overall. The relationship of the plasma VEGF levels with OS and progression-free survival (PFS), the patients were divided in the two groups based on their median VEGF value. The OS differed significantly between the low and high posttreatment VEGF levels (25.6 months vs. 13.4 months, P = 0.0284). No other relationship was found with plasma VEGF levels. It is known that most cytotoxic chemotherapeutics decrease the platelet count. In this study, thrombocytopenia was developed in 27.3% patients treated with bevacizumab plus chemotherapy. The association between VEGF levels and thrombocytopenia was not reported. Also, it is possible that platelet counts decreased with chemotherapy, but remained within normal limits. Because platelet counts before and after therapy has not been reported, the possible contribution of platelets on the decreasing VEGF levels remains obscure. We believe that the decrease in serum VEGF levels may at least in part be due to decreased platelet counts secondary to chemotherapy, and plasma VEGF levels may not accurately reflect the truth all the time before correcting the VEGF levels for platelet counts. M. A. N. Şendur S. Aksoy (&) Ş. Yaman Z. Arik N. Y. Ozdemir N. Zengin Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey e-mail: saksoy07@yahoo.com

Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis

Vascular endothelial growth factor (VEGF) is a potent angiogenesis mediator. Scant reports are available defining the role of VEGF in active and inactive tubercular meningitis (TBM) with no studies on brain tuberculoma. We quantified VEGF levels by enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) and serum in 20 cases each with active and inactive TBM as well as 22 cases of intraparenchymal tuberculoma. VEGF expression and microvessel angiogenesis quantification was done in 7 cases where tuberculomas were excised. Significantly increased VEGF levels in CSF were found in active TBM cases (106.0+/-50.0 pg/ml) compared to inactive TBM cases (14.7+/-10.0 pg/ml) (p<0.001). Mean serum VEGF levels in active TBM, inactive TBM and tuberculoma were 694.93+/-820.66 pg/ml, 499.61+/-238.33 pg/ml and 541.0+/-389.0 pg/ml, respectively. Immunohistochemical staining of excised tuberculoma demonstrated high expression of VEGF in granulomatous areas with intense positivity in inflammatory mononuclear cells, Langhan's giant cells as well as reactive astrocytes and fibrocytes. A strong positive correlation was observed between microvessel density and VEGF expression. Serial decrease in serum VEGF levels was observed with increasing duration of therapy in tuberculoma. We conclude that increased CSF and serum VEGF levels are a measure of activity of the disease in neurotuberculosis and its gradual decrease over a period of time is probably an indicator of therapeutic response.

Failure of Treatment with Anti-VEGF Monoclonal Antibody for Long-standing POEMS Syndrome

We present the case of a 71-year-old woman with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. Overproduction of vascular endothelial growth factor (VEGF), secreted by plasmacytoma, is considered responsible for the characteristic symptoms, and therefore anti-VEGF monoclonal antibody (bevacizumab) could be a therapeutic option. The patient was treated with bevacizumab 7 years after onset. Despite a dramatic decrease in serum VEGF levels, there was no clinical improvement, possibly because aberrant angiogenesis had already developed systemically. We suggest that careful consideration should be taken for indication of bevacizumab therapy, and this agent may be used in selected patients with a short duration POEMS syndrome.

Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients.

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that participates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0.051, P < 0.05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0.05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0.05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

Circulating vascular endothelial growth factor in patients with colorectal cancer.

The expression of vascular endothelial growth factor (VEGF), a glycoprotein that selectively promotes proliferation of endothelial cells, has been associated with cancer development. The aim of the present study was to determine whether serum levels of VEGF correlate with disease progression in patients with colorectal cancer. VEGF levels were measured by a highly sensitive enzyme-linked immunosorbent assay in sera from 67 patients with colorectal cancer, 14 patients with colorectal adenomas, and 72 healthy volunteers, and in tissue homogenates from 10 patients with colorectal cancer. Serum VEGF levels were significantly higher in patients with colorectal cancer than in patients with colorectal adenomas or in normal controls (p < 0.01). In patients with colorectal cancer, serum VEGF levels were significantly associated with Dukes stage (p < 0.01) and with carcinoembryonic antigen levels (r = 0.725, p < 0.001). Patients with hepatic and/or lymph node metastasis had higher serum VEGF levels than those without. Surgical resection of the colorectal tumor led to a decrease in serum VEGF levels whether or not metastasis was present (p < 0.05). The tumor-bearing tissue contained significantly more VEGF than normal-appearing mucosa (p < 0.05). VEGF is involved in the development of colorectal cancer. Measurement of VEGF in the serum may be a useful noninvasive clinical marker for evaluating the disease status.