Different vascular endothelial growth factor (VEGF), VEGF‐receptor 1 and ‐2 mRNA expression profiles between clear cell and papillary renal cell carcinoma

Ljungberg, Börje; Jacobsen, Jan; Rudolfsson, Stina Häggström; Lindh, Gudrun; Grankvist, Kjell; Rasmuson, Torgny

doi:10.1111/j.1464-410x.2006.06387.x

Cited by 46 publications

(29 citation statements)

References 26 publications

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“…Our findings of an association between high VEGF-R1 and -R2 levels in tumor cells and decreased survival are contrary to those of Ljungberg et al, 11 who assessed mRNA levels of these receptors in 104 patients. The difference might be related to sample size, inconsistencies between mRNA and protein levels and inclusion of stromal elements when performing RT-PCR on snap-frozen specimens.…”

Section: Discussioncontrasting

confidence: 57%

“…Other smaller studies assessing VEGF/VEGF-Rs and microvessel density have been conducted. [9][10][11] Jacobsen et al 12 assessed a relatively large cohort tissue microarray (TMA) for VEGF expression, but no assessment of VEGF-R expression and microvessel density was made. Our purpose was to assess expression of VEGF, VEGF-R1, VEGF-R2 and VEGF-R3 in three tissue components: RCC cells, endothelial cells and adjacent normal renal tissue on a large patient cohort with associated clinical/ pathological data.…”

mentioning

confidence: 99%

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Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Kluger

Siddiqui

Angeletti

et al. 2008

Laboratory Investigation

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Section: Discussioncontrasting

confidence: 57%

mentioning

confidence: 99%

Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Kluger

Siddiqui

Angeletti

et al. 2008

Laboratory Investigation

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“…Clinically, Ljungberg et al demonstrated that the mRNA levels of VEGF, VEGF-receptor Type 1 and VEGF-receptor Type 2 above the median were related to adverse survival in papillary RCC. 29 Therefore, it is relevant to measure VEGF in a clear or non-clear cell RCC model.…”

Section: Cancer Therapy 680mentioning

confidence: 99%

Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function

Maita

Yuasa

Tsuchiya

et al. 2011

Intl Journal of Cancer

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We investigated the inhibitory effect of sunitinib, a newly approved multitargeted tyrosine kinase inhibitor, against the progression of renal cell cancer (RCC) bone metastases in vivo. In vitro cell proliferation was determined using the MTS assay. To investigate the inhibitory effects of sunitinib in vivo, we established luciferase-labeled ACHN Luc cells derived from papillary RCC. Mice in which ACHN Luc cells had been transplanted into the left ventricle to establish bone metastases were treated orally with 40 mg/kg/day sunitinib or vehicle control for 3 weeks. Growth of the cancer cells was monitored using an in vivo imaging system. In addition, 16 patients with metastatic RCC were treated with sunitinib, and serum and urine levels of amino-terminal telopeptide (NTx) were measured as markers of bone resorption. Sunitinib did not inhibit the growth of RCC cells in vitro at clinically or experimentally achievable serum levels (100 nM-1 lM). To investigate the inhibitory effect of sunitinib in vivo, we established luciferase-labeled human RCC cells (ACHN Luc ). Sunitinib prevented the growth of ACHN Luc RCC cells in the bone metastatic mouse model. The number of osteoclasts in sunitinib-treated mice was significantly less than that in control mice. Serum and urine levels of NTx in patients with metastatic RCC declined significantly during the first 4 weeks of sunitinib treatment (p 5 0.027). Sunitinib is a potent anticancer agent for RCC bone metastases, at least for papillary RCC.Bone is a common site of metastasis, with the frequency of solitary or multiple metastases to bone ranging from 24 to 51% in patients with metastatic renal cell cancer (RCC). 1-3 Although bone metastasis is not an independent prognostic factor associated with poor survival, the prognosis of patients with bone metastasis is not favorable when they are treated with cytokines, with an average life expectancy of 8-16 months. [2][3][4] Moreover, bone metastases are associated with poor performance status due to intractable pain and pathological fractures. 5 Because treatment options for RCC patients with bone metastasis are limited, appropriate treatment strategies are desired.Sunitinib is a newly approved, multitarget, small-molecule tyrosine kinase inhibitor for the treatment of metastatic RCC. It inhibits various receptor tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; stem cell factor receptor (KIT) and PDGF receptors a and b. 6-8 Moreover, sunitinib has been known to inhibit the phosphorylation of colony-stimulating factor (CSF)-1R, resulting in the prevention of osteoclast function and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. 9,10 These findings led us to propose the hypothesis that sunitinib may inhibit tumor growth and osteolysis in bone metastatic lesions in RCC patients.Although establishing a treatment strategy for bone metastases from RCC is important for urologists, the assessment of inhibitory effects on the growth of bone metastases is oft...

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“…Different RCC types may have dissimilar expression patterns of VEGF and receptor mRNA levels. In clear cell RCC, VEGFR-2 levels were higher in stage I-II than in more advanced stages, while in papillary RCC, VEGF and VEGFR-2 levels were higher in stage III than in stage I-II tumors (Ljungberg et al 2006). In another report, the VEGFR-2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%) (Badalian et al 2007).…”

Section: Kidney Cancermentioning

confidence: 90%

Regulation of Angiogenesis in Human Cancer via Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2)

Guo¹,

Colbert²,

McGlothen³

et al. 2012

Tumor Angiogenesis

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Different vascular endothelial growth factor (VEGF), VEGF‐receptor 1 and ‐2 mRNA expression profiles between clear cell and papillary renal cell carcinoma

Abstract: available from the tumours (53 women and 57 men, mean age 64.7 years, range 25-85).

Cited by 46 publications

References 26 publications

Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function

Regulation of Angiogenesis in Human Cancer via Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2)

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