Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene

Rastinejad, Farzan; Polverini, Peter J.; Bouck, Noël

doi:10.1016/0092-8674(89)90238-9

Cited by 427 publications

(205 citation statements)

References 54 publications

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“…These results are consistent with current knowledge about p16 as a negative regulator of cell-cycle progression. The complexity of the cancercontrol pathways of tumor-suppressor genes, however, involves other aspects of the biology of the tumors (Rastinejad et al, 1989;Merzak et al, 1994;Van Meir et al, 1994;Hsu et al, 1996), in addition to blocking cell-cycle progression. In this regard, it has been reported that inactivation of p16 correlates with high invasive stage in melanomas, indicating that loss of p16 possibly provides a selective advantage for the development of invasive cells (Reed et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated p16/CDKN2 gene transfer suppresses glioma invasion in vitro

et al. 1997

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Malignant gliomas extensively in®ltrate the surrounding normal brain, and their di use invasion is one of the most important barriers to successful therapy. Recent studies indicate that the progression of gliomas from lowgrade to high-grade may depend on the acquisition of a new phenotype and the subsequent addition of genetic defects. One of the most frequent abnormalities in the progression of gliomas is the inactivation of tumorsuppressor gene p16, suggesting that loss of p16 is associated with acquisition of malignant characteristics. Consistent with this hypothesis, our previous studies showed that restoring wild-type p16 activity into p16-null malignant glioma cells modi®ed their phenotype. In order to understand whether the biological consequences of p16 inactivation in high-grade gliomas included facilitating invasiveness, we used a recombinant replication-de®cient adenovirus carrying the cDNA of the p16/CDKN2 gene to infect and express high levels of p16 protein in p16-null SNB19 glioma cells. Invasion of SNB19 glioma cells was tested into two models: invasion of glioma cells through Matrigel-coated transwell inserts and invasion of tumor-cell spheroids into fetal rat-brain aggregates in a co-culture system. Matrigel invasion assays showed that the SNB19 cells expressing exogenous p16 exhibited signi®cantly reduced invasion. Similarly, invasion of p16-treated SNB19 cells into fetal rat-brain aggregates was reduced during a 72 h time period compared to invasion of the adenovirus-control and mock-infected cells. Expression of matrix metalloproteinase-2 (MMP-2), an enzyme involved in tumor-cell invasion, in SNB19 cells expressing p16 was signi®cantly reduced compared to that of parental SNB19 and vector-infected cells. Our results show that restoring wild-type p16 activity into p16-null SNB19 glioma cells signi®cantly inhibits tumorcell invasion, thus suggesting a novel function of the p16 gene.

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated p16/CDKN2 gene transfer suppresses glioma invasion in vitro

et al. 1997

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“…30 In experimental tumor models, the progression of neoplastic disease is similarly accompanied by an inhibition of the rate of new vessel formation. 31 This phenomenon may reflect the influence of antiangiogenic factors, 32 the inadequacy of the angiogenic mechanisms to support the viability of a growing neoplasm, or a gradual restriction of the neoplastic cells' metabolic demands. 27 Experimental and histologic data suggest that angiogenesis may be induced as early as during the transition of hyperplasia to neoplasia.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications

et al. 2005

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The significance of angiogenesis in Hodgkin's lymphoma (HL) is not well defined. The aim of this study was to evaluate various morphometric characteristics of microvessels in lymph node sections of 286 patients with HL at diagnosis and investigate their relationship with clinicopathologic parameters and prognosis. Microvessel density (MVD), total vascular area (TVA) and several size-and shape-related microvascular parameters were quantitated -after anti-CD34 immunohistochemical staining -in the region of most intense vascularization, using image analysis. An increase in microvessel caliber parameters (area, perimeter, major and minor axis length) and a decrease in MVD were noted with increasing stage. An inverse relationship was recorded between MVD and the number of involved sites (NIS) and LDH. In univariate analysis, overall disease-specific survival was adversely affected by MVD and TVA, whereas inferior failure-free survival (FFS) was associated with the presence of more flattened vessel sections. Multivariate analysis disclosed that the extent of angiogenesis (MVD/ TVA), age and the NIS independently affected overall survival. Accordingly, FFS was independently linked to the shape of microvessels and albumin levels or the NIS. In conclusion, our data support the view that angiogenesis in HL provides independent prognostic information, requiring the concomitant evaluation of quantitative and qualitative aspects of microvascular network.

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“…20 Several molecules that exhibit inhibitory effects on endothelial cell growth were recently reported. 9,[21][22][23][24][25] Treatment with their recombinant proteins, such as angiostatin and endostatin, demonstrated the inhibition of tumor growth. However, there are several limitations to clinical use of the recombinant protein treatment.…”

Section: Was Apparently Inhibited In the Treatment With Psectag2b-vasmentioning

confidence: 99%