Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression

Lee, Ji Shin; Kim, Hyung Seok; Jung, Jong Jae; Park, Chang Soo; Lee, Min Cheol

doi:10.1002/jso.1066

Cited by 44 publications

(35 citation statements)

References 23 publications

(21 reference statements)

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“…remaining 42 articles were reviewed, and of these 23 were excluded, the reasons for which are shown in Figure 1. Thus, 19 studies were included in the quantitative synthesis [10,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. Five of these studies [20,22,25,33,36] did not provide data (HR or Kaplan-Meier curve) to calculate the HR for OS, PFS, or DSS, and therefore could not be included in the meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Five studies that were included in the qualitative synthesis did not provide sufficient data for calculating a HR, and thus were not included in the meta-analysis. Three earlier studies showed that a normal tumor necrosis factor (TNF)-α level, but not VEGF, was prognostic for patients with RCC [36], VEGF expression in RCC tumor tissue was not prognostic [33], and in pRCC MIB-1, VEGF, CD31, and c-met oncogenic protein were not prognostic, while Fuhrman grade was an independent predictor of survival [25]. A more recent study examined CD147 and VEGF expression in paraffin-embedded specimens from 53 patients with advanced RCC and 12 healthy controls, and reported that patients who were CD147−/VEGF− had the best outcomes, while patients who were CD147+/VEGF+ had the worst [22].…”

Section: Discussionmentioning

confidence: 99%

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

Shen

Liu

et al. 2017

CIM

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Objective: 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.Methods: 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).Results: 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). Conclusion: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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Shen

Liu

et al. 2017

CIM

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“…Accordingly, the relationship between p53 abnormalities and VEGF upregulation has been explored in human solid neoplasms. Evidence for this fine interplay was not always detected [21][22][23][24][25][26] and even when the p53 status was evaluated at the molecular level, loss of wild-type p53 did not always correlate with increased VEGF expression [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

“…Current data suggest a functional control of wild-type p53 on VEGF [7,9], and a correlation between the p53 status and the VEGF expression has been explored in human solid neoplasms [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Tumors with a loss of wild-type p53 or p53 overexpression showed VEGF upregulation [10][11][12][13][14][15][16][17][18][19][20]; however, this close relationship was not always found [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor and p53 Expressions in Liver and Abdominal Metastases from Colon Cancer

Cascinu¹,

Graziano²,

Catalano³

et al. 2003

Tumor Biol

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Objective: To determine the relationship between p53 overexpression and vascular endothelial growth factor (VEGF) upregulation in liver and abdominal metastases from colon cancer. The analysis in the two metastatic sites was carried out to evaluate the potential role of microenvironment in the molecular regulation of VEGF. Methods: Bioptic specimens of liver and abdominal metastases from colon carcinomas were examined by immunohistochemistry for p53 and VEGF expressions. Consecutive cases with assessable tumor tissue were selected. Results: The study population consisted of 24 cases having liver metastases and 34 cases having abdominal metastases. Abdominal metastases showed a higher number of VEGF-positive cases and a higher intensity of VEGF immunoreactivity than liver metastases did (p = 0.01). The combined analysis of p53 and VEGF showed a strong association between the two markers in the 24 liver metastases; 9 cases were VEGF positive/p53 positive and 15 cases were VEGF negative/p53 negative. This relationship was not found in the 34 abdominal metastases, which showed concordance between the two markers in 9 VEGF-positive/p53-positive cases only. Conclusions: Microenvironment factors like hypoxia may have a predominant role in inducing VEGF expression and they can override the molecular control of p53 on VEGF.

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“…Strong correlations have also been documented between VEGF up-regulation in RCC tumors with nuclear grade and TNM stage [Paradis et al, 2000;Lee et al, 2001] as well as a poor prognostic outcome [Paradis et al, 2000]. The majority of RCC tumors harboring a VHL mutation express HIF that significantly correlates with elevated VEGF [Na et al, 2003].…”

Section: Kidney Cancermentioning

confidence: 99%

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

Sakamoto

Ryan

Kyprianou

2007

J of Cellular Biochemistry

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Recent advances toward understanding the molecular mechanisms regulating cancer initiation and progression provide new insights into the therapeutic value of targeting tumor vascularity by interfering with angiogenic signaling pathways. The functional contribution of key angiogenic factors toward increased vascularity characterizing metastatic tumors and their therapeutic exploitation is considered in three major urologic malignancies, renal, bladder, and prostate cancer. With the realization that the success of the therapeutic efficacy of the various anti-angiogenic approaches for the treatment of urologic tumors has yet to be proven clinically, the challenge remains to select critical angiogenesis pathways that can be targeted for an individual tumor. Here we discuss the major mechanisms that support formation of vasculature in renal, bladder, and prostate tumors and the current results of targeting of specific molecules/regulators for therapeutic intervention against metastastic disease. Keywordsvascularity; tumor growth; apoptosis; VEGF; bladder cancer; renal cancer; prostate cancer In 2007, there will be an estimated 346,440 new cases diagnosed with urologic cancer in the United States and 54,360 Americans will die from a urologic malignancy (SEER Cancer Statistics Review, http://cancernet.nci.nih.gov/statistics). This mortality rate is alarmingly high as it translates to one individual dying every 9 min in the US due to a urologic tumor and thus a significant health issue.Angiogenesis is an essential process in normal physiological functions such as ovarian cycle in female reproductive system [Kaczmarek et al., 2005] and a contributing factor in disease states such as chronic inflammation, arthritis, cancer, and macular degeneration . During the development of the embryo, mesoderm differentiates into angioblasts; these endothelial cells, not yet organized into a lumen, form primitive vessels toward development of blood vessel network, via vasculogenesis. In the adult, new blood vessels form from preexisting vasculature, via angiogenesis [Risau, 1997], while malignant conditions induce a hypercoagulable state in their hosts [Nash et al., 2001]. By early 1960s it was evident that tumors could elaborate diffusible substances that induce angiogenesis from the host vasculature [Algira et al., 1945;Greenblatt and Shubick, 1968]. The increased tumor vascularity was originally believed to be vasodilation of the host endothelium in response to metabolic waste products from within the tumor . A decade later Dr. Folkman's pioneering work identified angiogenesis as a required phenomenon for tumor growth and metastasis, first defining the potential therapeutic value of agents targeting this process , 1971]. Tumor blood vessels exhibit characteristic markers which are not present in normal angiogenic tissues . After enduring the circulation "journey," metastatic cancer cells can escape out of the endothelial vasculature and in the target tissue via extravasation. How do the metastastic cells signal activa...

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Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression

Abstract: Our data do not show a direct regulation of VEGF expression by p53. We suggest that VEGF expression plays a role in the promotion of angiogenesis in RCC.

Cited by 44 publications

References 23 publications

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

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 and p53 Expressions in Liver and Abdominal Metastases from Colon Cancer

Targeting vasculature in urologic tumors: Mechanistic and therapeutic significance

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