Limits...
GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m-ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor-β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)-1 and −2, and platelet-derived growth factor receptor-α and -β] in primary RCC specimens were assessed by immunohistochemical staining. The expression levels of GLI2, VEGFR-1, VEGFR-2 and pre-treatment C-reactive protein as well as the Memorial Sloan-Kettering Cancer Center risk were identified as significant predictors of progression-free survival (PFS). Of these, only GLI2 expression was independently correlated to PFS according to multivariate analysis. Furthermore, treatment with sunitinib resulted in a marked inhibition of GLI2 expression in the parental human RCC ACHN cell line, but not in ACHN cells with acquired resistance to sunitinib. These findings suggested that GLI2 may be involved in the acquisition of resistance to sunitinib in RCC; thus, it may be useful to consider the expression levels of GLI2 in addition to conventional prognostic parameters when selecting m-ccRCC patients likely to benefit from treatment with sunitinib.

No MeSH data available.


Related in: MedlinePlus

Western blot analysis evaluating the expression levels of GLI2 and β-actin in ACHN/P and ACHN/R treated with or without 5 µM sunitinib. ACHN/P, parental ACHN glioma cell line; ACHN/R, ACHN cells with acquired sunitinib resistance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998152&req=5

f3-mco-0-0-950: Western blot analysis evaluating the expression levels of GLI2 and β-actin in ACHN/P and ACHN/R treated with or without 5 µM sunitinib. ACHN/P, parental ACHN glioma cell line; ACHN/R, ACHN cells with acquired sunitinib resistance.

Mentions: To further characterize the significance of GLI2 expression in RCC tissues with regard to the efficacy of sunitinib, changes in GLI2 expression in ACHN/P and ACHN/R cells cultured in the absence or presence of sunitinib were examined. As shown in Fig. 3, despite the lack of a significant difference in GLI2 expression between ACHN/P and ACHN/R in the absence of sunitinib, administration of sunitinib resulted in a marked downregulation of GLI2 in ACHN/P, but not in ACHN/R.


GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib
Western blot analysis evaluating the expression levels of GLI2 and β-actin in ACHN/P and ACHN/R treated with or without 5 µM sunitinib. ACHN/P, parental ACHN glioma cell line; ACHN/R, ACHN cells with acquired sunitinib resistance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998152&req=5

f3-mco-0-0-950: Western blot analysis evaluating the expression levels of GLI2 and β-actin in ACHN/P and ACHN/R treated with or without 5 µM sunitinib. ACHN/P, parental ACHN glioma cell line; ACHN/R, ACHN cells with acquired sunitinib resistance.
Mentions: To further characterize the significance of GLI2 expression in RCC tissues with regard to the efficacy of sunitinib, changes in GLI2 expression in ACHN/P and ACHN/R cells cultured in the absence or presence of sunitinib were examined. As shown in Fig. 3, despite the lack of a significant difference in GLI2 expression between ACHN/P and ACHN/R in the absence of sunitinib, administration of sunitinib resulted in a marked downregulation of GLI2 in ACHN/P, but not in ACHN/R.

View Article: PubMed Central - PubMed

ABSTRACT

The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m-ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor-β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)-1 and −2, and platelet-derived growth factor receptor-α and -β] in primary RCC specimens were assessed by immunohistochemical staining. The expression levels of GLI2, VEGFR-1, VEGFR-2 and pre-treatment C-reactive protein as well as the Memorial Sloan-Kettering Cancer Center risk were identified as significant predictors of progression-free survival (PFS). Of these, only GLI2 expression was independently correlated to PFS according to multivariate analysis. Furthermore, treatment with sunitinib resulted in a marked inhibition of GLI2 expression in the parental human RCC ACHN cell line, but not in ACHN cells with acquired resistance to sunitinib. These findings suggested that GLI2 may be involved in the acquisition of resistance to sunitinib in RCC; thus, it may be useful to consider the expression levels of GLI2 in addition to conventional prognostic parameters when selecting m-ccRCC patients likely to benefit from treatment with sunitinib.

No MeSH data available.


Related in: MedlinePlus