Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularisation in renal cell carcinoma

Tomisawa, Masashi; Tokunaga, Tetsuji; Oshika, Y; Tsuchida, Takashi; Fukushima, Yasushi; Sato, Hirotaka; Kijima, Hiroshi; Yamazaki, Hitoshi; Ueyama, Yoshito; Tamaoki, Norikazu; Nakamura, Masato

doi:10.1016/s0959-8049(98)00278-0

Cited by 119 publications

(97 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The VEGF isoform pattern was analysed in T9 kidney tumour tissue and normal kidney of the same patient by reverse transcription-polymerase chain reaction (RT-PCR) as described by Tomisawa et al (1999). In short, 1 µg total RNA was reversely transcribed using 100 ng dT 18 primer and VEGF cDNA fragments were amplified by 30 cycles of PCR consisting of 1 minute at 94˚C, 1 minute at 55˚C and 2 minutes at 72˚C, using the following primers: V-S: 5′-AGCCATCCTGTGTGCCCCTGATG-3′, V-S4: 5′-GGATCAAACCTCACCAAGGCC-3′, V-A: 5′-GCGAATTC-CTCCTGCCCGGCTCAC-3′, V-A7: 5′-CTTTCTCCGCTCT-GAGCAAGGC-3′.…”

Section: Vascular Endothelial Growth Factor (Vegf) Isoform Analysismentioning

confidence: 99%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 1.4% of cancer-related deaths (Reis and Faria, 1994). The prognosis of RCC remains poor. One third of the patients already have metastases when first consulting the hospital. Another 30-40% of patients develop metastases after surgical excision of the primary tumour (Ravaud and Debled, 1999). RCC are radioresistant (Nieder et al, 1996) and more than 80% are chemoresistant (Mickisch, 1994). Since RCC are presumed to be immunogenic, several clinical trials are exploring the efficacy of cytokines, mainly interleukin 2 (IL2) and/or interferon-α (IFNα), and the transfer of lymphokine-activated killer cells (Hofmockel et al, 1997;Bukowski, 2000;Hoffman et al, 2000). Despite these new options, the median survival time of patients with metastatic disease still remains only 6-8 months and the overall 5-year survival rate is less than 5% (Moch et al, 2000;Motzer and Russo, 2000). Thus, there is an urgent requirement for alternative therapeutic modalities.The current strategy is to design therapeutic approaches based on specific biological features of each tumour type. These include (i) the aberrant expression of genes which can be recognized by the immune system as foreign (Pawelec et al, 1999;Wang and Rosenberg, 1999;Bremers and Parmiani, 2000); (ii) gene products related to the formation of new blood vessels (neoangiogenesis), since they are essential for tumour expansion and metastatic settlement (Harris and Thorgeirsson, 1998;Kerbel, 2000;Rosen, 2000) and (iii) the altered expression of adhesion molecules, matrix-degrading enzymes, their receptors and inhibitors, which are a further requisite of metastatic spread (Huang et al, 1997;Yu et al, 1997).Several technique enable the identification of tumour markers. Subtractive hybridization (Lamar and Palmer, 1984; Kunkel et al, 1985;Kuang et al, 1998), differential display reverse transcription-polymerase chain reaction (DD RT-PCR; Liang and Pardee, 1992) and hybridization of cDNA microarrays (reviewed in Khan et al, 1999) are frequently used to compare the expression patterns between tumour and normal tissue. Other approaches, such as serological screening (SEREX;Sahin et al, 1995) and screening of cytotoxic T lymphocyte activity against an autologous tumour cell line (De Plaen et al, 1988), are especially focused on the identification of immunogenic tumour molecules.We have described recently the successful use of SSH using matched RCC and normal kidney tissue . In this study, we randomly selected 16 genes, which by SSH appeared to be differentially expressed. Differential expression of 9 of these 16 genes could be verified by Northern blot analysis. 2 of the 9 genes appeared to be novel. From the remaining 7 genes, expression of 5 had been associated with the malignant phenotype. To substantiate that SSH is a suitable method for the identification of differentially expressed genes, we performed a SSH with an additional pair of normal renal and RCC tissue and compared the validity of SSH ...

show abstract

Section: Vascular Endothelial Growth Factor (Vegf) Isoform Analysismentioning

confidence: 99%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Serum levels of VEGF often are elevated in RCC patients and VEGF mRNA levels in renal cell carcinoma have been reported to be higher than those found in surrounding normal tissues Berger et al, 1995). In addition, elevated serum/urine VEGF levels have been shown to associated with malignant progression and poor treatment outcome (Sato et al, 1994;Baccala et al, 1998;Tomisawa et al, 1999;Ishizuka et al, 2000;Jacobsen et al, 2000). Taken together, these findings suggest that VEGF is one of the important factors involved in the angiogenesis of RCC.…”

mentioning

confidence: 97%

Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor

Shi

Siemann

2002

Br J Cancer

View full text Add to dashboard Cite

Angiogenesis is critical for growth and metastatic spread of solid tumours. It is tightly controlled by specific regulatory factors. Vascular endothelial growth factor has been implicated as the key factor in tumour angiogenesis. In the present studies we evaluated the effects of blocking vascular endothelial growth factor production by antisense phosphorothioate oligodeoxynucleotides on the growth and angiogenic activity of a pre-clinical model of renal cell carcinoma (Caki-1). In vitro studies showed that treating Caki-1 cells with antisense phosphorothioate oligodeoxynucleotides directed against vascular endothelial growth factor mRNA led to a reduction in expressed vascular endothelial growth factor levels sufficient to impair the proliferation and migration of co-cultured endothelial cells. The observed effects were antisense sequence specific, dose dependent, and could be achieved at a low, non-toxic concentration of phosphorothioate oligodeoxynucleotides. When vascular endothelial growth factor antisense treated Caki-1 cells were injected into nude mice and evaluated for their angiogenic potential, the number of vessels initiated were approximately half that induced by untreated Caki-1 cells. To test the anti-tumour efficacy of vascular endothelial growth factor antisense, phosphorothioate oligodeoxynucleotides were administrated to nude mice bearing macroscopic Caki-1 xenografts. The results showed that the systemic administration of two doses of vascular endothelial growth factor antisense phosphorothioate oligodeoxynucleotides given 1 and 4 days after the tumours reached a size of *200 mm 3 significantly increased the time for tumours to grow to 1000 mm 3 .

show abstract

“…Heparins, especially NAC-HCPS, can effectively bind to various adhesive proteins such as fibronectin, laminin and collagen, and thus may affect cell adhesion and tubular formation. Finally, NAC-HCPS markedly reduced the number of CD34-positive vessels (a marker of microvascular endothelial cells) in subcutaneous 3LL tumours (Tomisawa et al, 1999;Oshika et al, 2000). The above results demonstrate that NAC-HCPS with its reduced anticoagulant property has a strong anti-angiogenesis.…”

Section: Discussionmentioning

confidence: 60%

“…To evaluate the microvessel density of the tumour, CD34 as an endothelial cell (vessel) marker was stained by an indirect method (Tomisawa et al, 1999;Oshika et al, 2000). After each section (4 mm thick) was dehydrated and treated with 0.6% hydrogen peroxide in methanol for 45 min, slides were autoclaved for antigen retrieval (1218C 15 min).…”

Section: Vascularity Of the Tumourmentioning

confidence: 99%

“…To evaluate the effect of NAC-HCPS on anti-angiogenesis, immuno-histochemical staining of murine CD34 of NAC-HCPS treated and control tumours of 3LL cells were carried out (Tomisawa et al, 1999;Oshika et al, 2000). Representative microphotographs of CD34 immuno-localisation in controls (PBS-treated) and NAC-HCPS treated subcutaneous induced tumours are shown in Figure 9A,B.…”

Section: Effect Of Nac-hcps On Vascularity Of the Tumour In Vivomentioning

confidence: 99%

See 1 more Smart Citation

Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

et al. 2002

View full text Add to dashboard Cite

Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant heparin-carrying polystyrene on tumour growth and metastasis. Non-anticoagulant heparin-carrying polystyrene has a higher activity to inhibit vascular endothelial growth factor-165-, fibroblast growth factor-2-or hepatocyte growth factor-induced human microvascular endothelial cell growth than heparin, ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin, which is probably due to the heparin-clustering effect of non-anticoagulant heparin-carrying polystyrene. Non-anticoagulant heparin-carrying polystyrene inhibited human microvascular endothelial cell, B16 melanoma and Lewis lung cancer cell adhesion to Matrigel-coated plates. Non-anticoagulant heparin-carrying polystyrene also showed strong inhibitory activities in the tubular formation of endothelial cells on Matrigel and B16-melanoma and Lewis lung cancer cell invasion in a Matrigel-coated chamber assay. In vivo studies showed that growth of subcutaneous induced tumours and lung metastasis of B16-melanoma and Lewis lung cancer cells were more effectively inhibited by non-anticoagulant heparin-carrying polystyrene than ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin. Furthermore, non-anticoagulant heparin-carrying polystyrene markedly reduced the number of CD34-positive vessels in subcutaneous Lewis lung cancer tumours, indicating a strong inhibition of angiogenesis. These results suggest that non-anticoagulant heparin-carrying polystyrene has an inhibitory activity on angiogenesis and tumour invasion and may be very useful in cancer therapy.

show abstract

Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularisation in renal cell carcinoma

Cited by 119 publications

References 19 publications

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor

Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

Contact Info

Product

Resources

About