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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 tumour cell apoptosis in vivo. Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the A498 renal cancer cell line. The control group received control antibody alone. (A) To detect apoptosis, a TUNEL assay was performed. The average number of TUNEL-positive cells was scored in 10 randomly selected microscopic fields. Vinorelbine as a single therapeutic agent and in combination with 2C3 caused significant tumour cell apoptosis. *, P < 0.05 and **, P < 0.01(treated group versus control group). (B) TUNEL-positive nuclei in different treatment groups. (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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fig07: Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on tumour cell apoptosis in vivo. Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the A498 renal cancer cell line. The control group received control antibody alone. (A) To detect apoptosis, a TUNEL assay was performed. The average number of TUNEL-positive cells was scored in 10 randomly selected microscopic fields. Vinorelbine as a single therapeutic agent and in combination with 2C3 caused significant tumour cell apoptosis. *, P < 0.05 and **, P < 0.01(treated group versus control group). (B) TUNEL-positive nuclei in different treatment groups. (A) Control group received only control antibody (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.

Mentions: To further investigate the mechanism of the observed tumour-suppressive activities, we examined the effect of vinorelbine alone and in combination with 2C3 on A498 tumour cell apoptosis in vivo with the TUNEL assay (Fig. 7A and B). The average number of TUNEL-positive cells measured in 10 randomly selected microscopic fields in different treatment groups was calculated. A significant increase in the number of apoptotic cells was observed in the group treated with vinorelbine alone (P < 0.01, compared to the control group) and in the combination treatment group (P < 0.01, treated group versus control group) (Fig. 7A).


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 tumour cell apoptosis in vivo. Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the A498 renal cancer cell line. The control group received control antibody alone. (A) To detect apoptosis, a TUNEL assay was performed. The average number of TUNEL-positive cells was scored in 10 randomly selected microscopic fields. Vinorelbine as a single therapeutic agent and in combination with 2C3 caused significant tumour cell apoptosis. *, P < 0.05 and **, P < 0.01(treated group versus control group). (B) TUNEL-positive nuclei in different treatment groups. (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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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2992850&req=5

fig07: Effect of vinorelbine alone and in combination with VEGF antibody 2C3 on tumour cell apoptosis in vivo. Nude mice were treated with vinorelbine, 2C3, or vinorelbine in combination with 2C3 after subcutaneous injection of the A498 renal cancer cell line. The control group received control antibody alone. (A) To detect apoptosis, a TUNEL assay was performed. The average number of TUNEL-positive cells was scored in 10 randomly selected microscopic fields. Vinorelbine as a single therapeutic agent and in combination with 2C3 caused significant tumour cell apoptosis. *, P < 0.05 and **, P < 0.01(treated group versus control group). (B) TUNEL-positive nuclei in different treatment groups. (A) Control group received only control antibody (B) received vinorelbine only, (C) received 2C3 only and (D) received both vinorelbine and 2C3.
Mentions: To further investigate the mechanism of the observed tumour-suppressive activities, we examined the effect of vinorelbine alone and in combination with 2C3 on A498 tumour cell apoptosis in vivo with the TUNEL assay (Fig. 7A and B). The average number of TUNEL-positive cells measured in 10 randomly selected microscopic fields in different treatment groups was calculated. A significant increase in the number of apoptotic cells was observed in the group treated with vinorelbine alone (P < 0.01, compared to the control group) and in the combination treatment group (P < 0.01, treated group versus control group) (Fig. 7A).

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