Clinicopathological characteristics of vascular endothelial growth factor expression in uveal melanoma: A meta-analysis

Yang, Meng; Kuang, Xiaocong; Pan, Yu; Tan, Meile; Lu, Binzhu; Lü, Jian; Cheng, Qiumei; Li, Jianmin

doi:10.3892/mco.2014.247

Cited by 13 publications

(12 citation statements)

References 21 publications

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“…In several types of cancer (colon carcinoma, soft tissue sarcomas and gastric cancer), serum VEGF level is a marker for disease stage and an indicator of metastasis. VEGF level is significantly elevated in uveal melanoma patients with metastatic disease compared to patients without metastases (70). In our previous studies, we injected nude mice with RUNX3 stably expressed prostate cancer cells and our results showed reduced angiogenesis and metastasis in vivo.…”

Section: Runx3 In Angiogenesismentioning

confidence: 52%

The emerging role of RUNX3 in cancer metastasis (Review)

et al. 2015

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Metastasis remains the major driver of mortality in patients with cancer. The multistep metastatic process starts with the dissemination of tumor cells from a primary site and leading to secondary tumor development in an anatomically distant location. Although significant progress has been made in understanding the molecular characteristics of metastasis, many questions remain regarding the intracellular mechanisms governing transition through the various metastatic stages. The runt-related transcription factor 3 (RUNX3) is a downstream effector of the transforming growth factor-β (TGF-β) signaling pathway, and has critical roles in the regulation of cell death by apoptosis, and in angiogenesis, epithelial-to-mesenchymal transition (EMT), cell migration and invasion. RUNX3 functions as a bona fide initiator of carcinogenesis by linking the Wnt oncogenic and TGF-β tumor suppressive pathways. RUNX3 is frequently inactivated in human cancer cell lines and cancer samples by hemizygous deletion of the Runx3 gene, hypermethylation of the Runx3 promoter, or cytoplasmic sequestration of RUNX3 protein. Inactivation of RUNX3 makes it a putative tumor suppressor in human neoplasia. In the present review, we summarize the proposed roles of RUNX3 in metastasis and, when applicable, highlight the mechanism by which they function.

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Section: Runx3 In Angiogenesismentioning

confidence: 52%

The emerging role of RUNX3 in cancer metastasis (Review)

et al. 2015

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“…Moreover, it is known that vascular endothelial growth factor (VEGF) expression appears to be greater in invasive malignant melanomas, suggesting a correlation between VEGF-induced angiogenesis and the aggressiveness of invasive melanomas [17].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, our study evaluated the distribution of p73, also known as tumor protein 73 (TP73), a member of the p53 family [17].…”

Section: Discussionmentioning

confidence: 99%

IL-17, IL-23, and p73 expression in cutaneous melanoma

Ganzetti¹,

Rubini

Campanati³

et al. 2015

Melanoma Research

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The incidence of cutaneous malignant melanoma is increasing worldwide, resulting in the demand for clinically useful prognostic biomarkers, especially for invasive and metastatic disease. We studied the immunohistochemical expression of interleukin-17 (IL-17), IL-23, and p73 in 35 malignant melanomas and compared them with benign melanocytic nevi and Spitz nevi, correlating them with clinical-pathological variables. A higher and statistically significant difference (P<0.05) in the intensity and percentage of stained cells of IL-17 and IL-23 was found in the melanoma group than in ordinary benign nevi that did not correlate with Breslow thickness nor Clark level. Moreover, p73 staining and percentage of stained cells was significantly higher (P<0.05) in all the melanomas studied, with a peculiar cytoplasmatic distribution. Our findings could suggest a possible IL-17, IL-23, and p73 involvement in cutaneous melanomas with a hypothetical impact on melanoma invasiveness.

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“…Die Bedeutung des Wachstumsfaktors VEGF für die Entwicklung des uvealen Melanoms ist nicht eindeutig. Allerdings zeigte eine Metaanalyse eine erhöhte Expression von VEGF in uvealen Melanomen, und auch in den tumorumgebenden Zellen und im Kam- merwasser von uvealen Melanompatienten tritt eine erhöhte VEGF-Expression auf [27][28][29]. Die Expression von VEGF ist für den angiogenen Phänotyp des uvealen Melanoms wichtig [30] und wird mit der Tumorvaskularisierung und Metastasen in Zusammenhang gebracht [31].…”

Section: Uveales Melanom Und Vegfunclassified

Uveale Melanomzellen unter oxidativem Stress – Einfluss von VEGF und VEGF-Inhibitoren

Dithmer

Kirsch

Gräfenstein

et al. 2017

Klin Monatsbl Augenheilkd

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The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation. Uveal melanoma is the most frequent primary tumour in the adult eye. For metastasis of this tumour, which affects about 50 % of the patients, no appropriate treatment is currently available. However, the primary tumour can efficiently be treated with ionizing radiation. A frequent side effect of this treatment is radiation retinopathy, which is treated with vascular endothelial growth factor (VEGF) antagonists. A therapy of the primary tumour with VEGF antagonists is under discussion. So far, little data is available on this subject, however, a paradoxical worsening of the situation has been found in a mouse model of uveal melanoma treated with bevacizumab. We have investigated the effect of VEGF and of the VEGF-antagonist bevacizumab on the survival of five different melanoma cell lines under oxidative stress treatment with hydrogen peroxide. In addition, we investigated the expression of relevant proteins and the effect of bevacizumab on the proliferation of the cells as well as its effect on the angiogenic behaviour of endothelial cells, co-cultured with uveal melanoma cells. Our study showed that not only VEGF but also, paradoxically, the VEGF-antagonist bevacizumab is able to protect uveal melanoma cells from oxidative stress-induced cell death. Bevacizumab did not influence the proliferation of the cells and showed only limited effectiveness to reduce angiogenic structures. Considering that oxidative stress is the mode of action for ionizing radiation to induce cell death, a protective effect of bevacizumab on uveal melanoma cells against oxidative stress is worrisome and argues against the use of VEGF in uveal melanoma.

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Clinicopathological characteristics of vascular endothelial growth factor expression in uveal melanoma: A meta-analysis

Cited by 13 publications

References 21 publications

The emerging role of RUNX3 in cancer metastasis (Review)

The emerging role of RUNX3 in cancer metastasis (Review)

IL-17, IL-23, and p73 expression in cutaneous melanoma

Uveale Melanomzellen unter oxidativem Stress – Einfluss von VEGF und VEGF-Inhibitoren

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