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VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma.

Sinha S, Cao Y, Dutta S, Wang E, Mukhopadhyay D - J. Cell. Mol. Med. (2008)

Bottom Line: For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC.We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice.The results suggest a breakthrough treatment for advanced RCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

ABSTRACT
Renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies and affects approximately three in 10,000 people. The impact of this disease produces about 31,000 new cases in the United States per year; and 12,000 people in the United States alone die from RCC annually. Although several treatment strategies have been investigated for RCC, this cancer continues to be a therapeutic challenge. For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC. We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice. Tumour angiogenesis was measured by vWF staining, and apoptosis was determined by the TUNEL assay. We observed a significant tumour growth inhibition when using a combinational therapy of anti-VEGF antibody 2C3 and vinorelbine in both A498 and 786-O tumour-bearing mice. The results suggest a breakthrough treatment for advanced RCC.

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Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on PCNA expression in vivo. (A) Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the renal cancer cell line A498. The control group received control antibody. Treatment of vinorelbine in vivo showed no considerable effect on PCNA expression. 2C3 alone or in combination with vinorelbine demonstrated a significant effect on the inhibition of the PCNA level. *, P < 0.05 (treated group versus control group). (B) PCNA-stained tumour sections. (A) Control group received only control antibody, (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.
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fig06: Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on PCNA expression in vivo. (A) Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the renal cancer cell line A498. The control group received control antibody. Treatment of vinorelbine in vivo showed no considerable effect on PCNA expression. 2C3 alone or in combination with vinorelbine demonstrated a significant effect on the inhibition of the PCNA level. *, P < 0.05 (treated group versus control group). (B) PCNA-stained tumour sections. (A) Control group received only control antibody, (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.

Mentions: To determine whether the observed tumour growth suppression was caused by inhibition of cell proliferation, we investigated the effect of vinorelbine alone and in combination with 2C3 on tumour cell proliferation as measured by proliferating cell nuclear antigen (PCNA) (Fig. 6A and B). The average number of PCNA-positive nuclei in 10 randomly selected microscopic fields is shown in Fig. 6A. No significant effect was observed in the inhibition of renal tumour cell proliferation in the vinorelbine-treated group compared to the control group in relation to PCNA expression. However, there was significant inhibition in PCNA expression in the vinorelbine and 2C3-treated group (P < 0.05, treated group versus control group).


VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma.

Sinha S, Cao Y, Dutta S, Wang E, Mukhopadhyay D - J. Cell. Mol. Med. (2008)

Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on PCNA expression in vivo. (A) Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the renal cancer cell line A498. The control group received control antibody. Treatment of vinorelbine in vivo showed no considerable effect on PCNA expression. 2C3 alone or in combination with vinorelbine demonstrated a significant effect on the inhibition of the PCNA level. *, P < 0.05 (treated group versus control group). (B) PCNA-stained tumour sections. (A) Control group received only control antibody, (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2992850&req=5

fig06: Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on PCNA expression in vivo. (A) Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the renal cancer cell line A498. The control group received control antibody. Treatment of vinorelbine in vivo showed no considerable effect on PCNA expression. 2C3 alone or in combination with vinorelbine demonstrated a significant effect on the inhibition of the PCNA level. *, P < 0.05 (treated group versus control group). (B) PCNA-stained tumour sections. (A) Control group received only control antibody, (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.
Mentions: To determine whether the observed tumour growth suppression was caused by inhibition of cell proliferation, we investigated the effect of vinorelbine alone and in combination with 2C3 on tumour cell proliferation as measured by proliferating cell nuclear antigen (PCNA) (Fig. 6A and B). The average number of PCNA-positive nuclei in 10 randomly selected microscopic fields is shown in Fig. 6A. No significant effect was observed in the inhibition of renal tumour cell proliferation in the vinorelbine-treated group compared to the control group in relation to PCNA expression. However, there was significant inhibition in PCNA expression in the vinorelbine and 2C3-treated group (P < 0.05, treated group versus control group).

Bottom Line: For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC.We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice.The results suggest a breakthrough treatment for advanced RCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

ABSTRACT
Renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies and affects approximately three in 10,000 people. The impact of this disease produces about 31,000 new cases in the United States per year; and 12,000 people in the United States alone die from RCC annually. Although several treatment strategies have been investigated for RCC, this cancer continues to be a therapeutic challenge. For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC. We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice. Tumour angiogenesis was measured by vWF staining, and apoptosis was determined by the TUNEL assay. We observed a significant tumour growth inhibition when using a combinational therapy of anti-VEGF antibody 2C3 and vinorelbine in both A498 and 786-O tumour-bearing mice. The results suggest a breakthrough treatment for advanced RCC.

Show MeSH
Related in: MedlinePlus