Prognostic significance of angiogenesis in human pancreatic cancer

Abstract

To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF -positive and 10 carcinomas (25.0%) were determined to be PD-ECGF -negative. In contrast, 27 carcinomas (67.5%) were evaluated to be VEGF -positive, whereas 13 carcinomas (32.5%) were VEGF -negative. VEGF gene expression was moderately associated with an increase in the IMD ( r 2 = 0.181, P = 0.006), but no significant relationship was found between PD-ECGF gene expression and the IMD ( r 2 = 0.093, P = 0.059). However, tumours with positive expression for both PD-ECGF and VEGF had a higher IMD ( P = 0.027). The results of the immunohistochemistry agreed well with the results of the quantitative RT-PCR. The median survival time of the hypervascular group was significantly shorter than that of the hypovascular group ( P < 0.0001). In comparing the survival according to PD-ECGF and VEGF gene expression, the median survival time of the patients with positive PD-ECGF expression was significantly shorter than those with negative PD-ECGF expression ( P = 0.040). Furthermore, the median survival time of the patients with positive VEGF expression was significantly shorter than those with negative VEGF expression ( P = 0.048). However, the Cox multivariate analysis indicated that the IMD and VEGF expression were independent prognostic factors of the various clinicopathologic variables in pancreatic cancer patients ( P = 0.0021 and P = 0.0443, respectively). © 1999 Cancer Research Campaign

Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer

“…13 Although considered as an hypovascular tumor, angiogenesis is nonetheless critical for the development and growth of PDAC. 27 In patients with such neoplasia, VEGFA expression in the tumor and high serum concentration are significantly correlated to a decreased median survival time 37,38 and to metastasis progression, especially to the liver. 28 The correlation between VEGFA expression and the survival remains significant even after a surgery putatively considered as curative.…”

Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice

“…32 The angiogenic properties of pancreatic cancer remain unclear, partially because pancreatic cancers have been considered hypovascular, based on roentgenographic findings. However, it has been shown that tumor angiogenesis is implicated in the rapid growth and metastasis of pancreatic cancer, 33 and some angiogenesis inhibitors efficiently inhibited tumor growth and metastasis of pancreatic cancer in experimental models. 34 -36 It was recently reported that NK4 is an angiogenesis inhibitor, which not only antagonizes HGFinduced angiogenesis but also abrogates the angiogenesis induced by other angiogenic inducers such as bFGF and vascular endothelial growth factor, and its antiangiogenic activity is likely to be exhibited through mechanisms distinct from its HGF -antagonist activity.…”

Effect of the vascular endothelial growth factor receptor‐2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice

“…12,30 Consequently, a variety of different inhibitors of VEGF activity have been developed, including humanized neutralizing anti-VEGF monoclonal antibodies, 31 soluble VEGF-Rs, 32 anti-sense VEGF mRNA expressing constructs, 33 VEGF-toxin conjugates, 34 and inhibitors of VEGF-R function. 35 Because VEGF is implicated in the angiogenesis of human pancreatic cancer 15,19,36 and VEGF expression has been shown to be associated with a poor prognosis in human pancreatic cancer, [37][38][39] we investigated the efficacy of a VEGF-R2 antibody, DC101, with or without gemcitabine on primary tumor growth and metastasis of human pancreatic cancers growing orthotopically in nude mice. Treatment with gemcitabine or DC101 alone resulted in an ϳ65% and ϳ70% reduction of primary pancreatic tumor volume, respectively, as compared to control.…”