Expression of PCNA, Basic Fibroblast Growth Factor, FGF-receptor and Vascular Endothelial Growth Factor in Adenomas and Carcinomas of Human Colon.

Shiraishi, A.; Ishiwata, Toshiyuki; Shoji, Tasuku; Asano, Gorō

doi:10.1267/ahc.28.21

Cited by 22 publications

(8 citation statements)

References 20 publications

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“…Previous studies have reported VEGF immunoreactivity in stromal cells in colon and ovarian cancers [16,17] . However, the biological role of stromal VEGF remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The Angiogenic Switch for Vascular Endothelial Growth Factor-A and Cyclooxygenase-2 in Prostate Carcinoma: Correlation with Microvessel Density, Androgen Receptor Content and Gleason Grade

Gyftopoulos¹,

Vourda²,

Sakellaropoulos

et al. 2011

Urol Int

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Objective: Angiogenesis is essential for tumor growth and metastasis; however, angiogenic factors are not uniformly expressed in prostate carcinoma. Our aim was to determine the expression of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) in prostate carcinomas in relation to intratumoral microvessel density (MVD), tumor grade and androgen receptor (AR) status. Materials and Methods: The expression of AR, VEGF-A and COX-2 was immunohistochemically evaluated in 24 benign prostatic hyperplasia (BPH) and 139 prostate carcinoma cases. MVD was evaluated by CD34 immunostaining. Results: Nuclear AR expression was inversely related to tumor grade (p < 0.001). MVD was strongly related to tumor grade, VEGF-A and COX-2 (p < 0.001 in all comparisons). VEGF-A expression increased with tumor grade (p < 0.01) and was inversely related to stromal AR expression. COX-2 was present in both BPH and prostate carcinoma, but its expression increased with tumor grade (p < 0.01). High-grade neoplasms presented low-to-moderate VEGF staining intensity compared to strong COX-2 expression. Conclusions: Both VEGF-A and COX-2 expression is positively correlated with tumor grade and MVD. However, in Gleason 8–10 tumors, VEGF expression is moderate while COX-2 immunostaining is intense, suggesting a possible switch in the role of these two angiogenic factors in poorly differentiated neoplasms.

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“…Previous studies have reported VEGF immunoreactivity in stromal cells in colon and ovarian cancers [16,17] . However, the biological role of stromal VEGF remains unclear.…”

Section: Discussionmentioning

confidence: 99%

The Angiogenic Switch for Vascular Endothelial Growth Factor-A and Cyclooxygenase-2 in Prostate Carcinoma: Correlation with Microvessel Density, Androgen Receptor Content and Gleason Grade

Gyftopoulos¹,

Vourda²,

Sakellaropoulos

et al. 2011

Urol Int

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“…Sections were incubated overnight at 4°C with anti-human VEGF polyclonal antibody in PBS containing 1% bovine serum albumin. Anti-human VEGF polyclonal antibody was a kind gift from T Ishiwata of the first Department of Joint Disease and Department of Pathology, Nippon Medical School, Tokyo, Japan (Shiraishi et al, 1995). After six rinses in PBS, sections were incubated for 40 min at room temperature with biotinylated anti-rabbit immunoglobulin G, followed by six washes with PBS, and reacted with an avidin-biotin system, using 0.03% 3,3'-diaminobenzide tetrahydrochloride for about 2 min as chromogen.…”

Section: Materials and Methods Clinical Materialsmentioning

confidence: 99%

In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis

Uchida

Shimada²,

Watanabe³

et al. 1998

Br J Cancer

102

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In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis S Uchida, Y Shimada, G Summary Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on oesophageal carcinoma and the connection between VEGF and p53. One hundred and nine resected oesophageal squamous cell carcinomas were examined. VEGF expression was analysed by immunohistochemical staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF positive. A significant correlation was found between the VEGF expression and both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001). With regard to p53, we compared the expression of VEGF with the mutation of p53, examined using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who we have reported previously. The VEGF expression was significantly correlated to p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density (MVD) was counted, and endothelial cells were stained immunohistochemically using anti-CD34 monoclonal antibody against 29 cases with invasion limited to the submucosal layer. The average MVD had a tendency to correlate to VEGF expression (P = 0.1626). The prognoses of patients with VEGFpositive primary tumours were significantly worse than for those with VEGF-negative primary tumours (P = 0.0077). We have assumed that VEGF contributes to aggressive characteristics in oesophageal carcinomas and that VEGF expression might be affected by p53 status.

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“…Several studies have shown that VEGF expression is increased in the progression from nonmalignant to malignant colon tumors (13 -15). In fact, the expression of this growth factor was highest in carcinomas followed by adenomas and was lowest in normal mucosa (15). Both microvessel density and expression of VEGF have been associated with progression of colorectal cancer, development of metastases, and a poor prognosis (16 -23).…”

Section: Introductionmentioning

confidence: 99%

Sequence-dependent inhibition of human colon cancer cell growth and of prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an inhibitor of VEGFR and EGFR tyrosine kinases

Troiani

Lockerbie

Morrow

et al. 2006

Molecular Cancer Therapeutics

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To date, clinical studies combining the new generation of targeted therapies and chemotherapy have had mixed results. Preclinical studies can be used to identify potential antagonism/synergy between certain agents, with the potential to predict the most efficacious combinations for further investigation in the clinical setting. In this study, we investigated the sequence-dependent interactions of ZD6474 with oxaliplatin in two human colon cell lines in vitro. We evaluated the in vitro antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and RET tyrosine kinase activity, and oxaliplatin using three combination schedules: ZD6474 before oxaliplatin, oxaliplatin before ZD6474, and concurrent exposure. Cell proliferation studies showed that treatment with oxaliplatin followed by ZD6474 was highly synergistic, whereas the reverse sequence was clearly antagonistic as was concurrent exposure. Oxaliplatin induced a G 2 -M arrest, which was antagonized if the cells were previously or concurrently treated with ZD6474. ZD6474 enhanced oxaliplatin-induced apoptosis but only when added after oxaliplatin. The sequence-dependent antitumor effects appeared, in part, to be based on modulation of compensatory prosurvival pathways. Thus, expression of total and active phosphorylated EGFR, as well as AKT and extracellular signal-regulated kinase, was markedly increased by oxaliplatin. This increase was blocked by subsequent treatment with ZD6474. Furthermore, the synergistic sequence resulted in reduced expression of insulin-like growth factor-I receptor and a marked reduction in secretion of vascular endothelial growth factor protein. ZD6474 in combination with oxaliplatin has synergistic antiproliferative properties in human colorectal cancer cell lines in vitro when oxaliplatin is administered before ZD6474.

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Expression of PCNA, Basic Fibroblast Growth Factor, FGF-receptor and Vascular Endothelial Growth Factor in Adenomas and Carcinomas of Human Colon.

Cited by 22 publications

References 20 publications

The Angiogenic Switch for Vascular Endothelial Growth Factor-A and Cyclooxygenase-2 in Prostate Carcinoma: Correlation with Microvessel Density, Androgen Receptor Content and Gleason Grade

The Angiogenic Switch for Vascular Endothelial Growth Factor-A and Cyclooxygenase-2 in Prostate Carcinoma: Correlation with Microvessel Density, Androgen Receptor Content and Gleason Grade

In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis

Sequence-dependent inhibition of human colon cancer cell growth and of prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an inhibitor of VEGFR and EGFR tyrosine kinases

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